The 2002 Official Patient's Sourcebook on Muscular Dystrophy

THE 2002 OFFICIAL PATIENT’S SOURCEBOOK on USCULAR YSTROPHY J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., ...

Author: James N. Parker | Philip M. Parker

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THE 2002 OFFICIAL PATIENT’S SOURCEBOOK

on

USCULAR YSTROPHY J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2002 by ICON Group International, Inc. Copyright Ó2002 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Tiffany LaRochelle Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended as a substitute for consultation with your physician. All matters regarding your health require medical supervision. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960The 2002 Official Patient’s Sourcebook on Muscular Dystrophy: A Revised and Updated Directory for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83210-2 1. Muscular Dystrophy-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem or as a substitute for consultation with licensed medical professionals. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors or authors. ICON Group International, Inc., the editors, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs or other materials, please contact us to request permission (e-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this sourcebook.

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Dedication To the healthcare professionals dedicating their time and efforts to the study of muscular dystrophy.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to muscular dystrophy. All of the Official Patient’s Sourcebooks draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this sourcebook. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany LaRochelle for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for the Official Patient’s Sourcebook series published by ICON Health Publications.

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About ICON Health Publications In addition to muscular dystrophy, Official Patient’s Sourcebooks are available for the following related topics: ·

The Official Patient's Sourcebook on Avascular Necrosis

·

The Official Patient's Sourcebook on Growth Plate Fractures

·

The Official Patient's Sourcebook on Osteogenesis Imperfecta

·

The Official Patient's Sourcebook on Osteoporosis

·

The Official Patient's Sourcebook on Scoliosis

·

The Official Patient's Sourcebook on Sjogren's Syndrome

·

The Official Patient's Sourcebook on Spinal Stenosis

To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

Contents vii

Table of Contents INTRODUCTION...................................................................................... 1

Overview............................................................................................................... 1 Organization......................................................................................................... 3 Scope ..................................................................................................................... 3 Moving Forward................................................................................................... 5

PART I: THE ESSENTIALS ................................................. 7 CHAPTER 1. THE ESSENTIALS ON MUSCULAR DYSTROPHY: GUIDELINES ........................................................................................... 9

Overview............................................................................................................... 9 What Is Muscular Dystrophy (MD)?................................................................ 10 Is There Any Treatment? ................................................................................... 11 What Is the Prognosis?....................................................................................... 11 What Research Is Being Done? .......................................................................... 11 More Guideline Sources ..................................................................................... 12 Vocabulary Builder............................................................................................. 18

CHAPTER 2. SEEKING GUIDANCE ....................................................... 21

Overview............................................................................................................. 21 Associations and Muscular Dystrophy .............................................................. 21 Finding More Associations................................................................................. 33 Finding Doctors.................................................................................................. 34 Selecting Your Doctor ........................................................................................ 36 Working with Your Doctor ................................................................................ 36 Broader Health-Related Resources ..................................................................... 38 Vocabulary Builder............................................................................................. 38

CHAPTER 3. CLINICAL TRIALS AND MUSCULAR DYSTROPHY ............................................................................................................. 41

Overview............................................................................................................. 41 Recent Trials on Muscular Dystrophy............................................................... 44 Benefits and Risks............................................................................................... 50 Keeping Current on Clinical Trials.................................................................... 53 General References.............................................................................................. 54 Vocabulary Builder............................................................................................. 55

PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL.................................................. 57 CHAPTER 4. STUDIES ON MUSCULAR DYSTROPHY ............................ 59

Overview............................................................................................................. 59 The Combined Health Information Database ..................................................... 59 Federally-Funded Research on Muscular Dystrophy ........................................ 63

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E-Journals: PubMed Central .............................................................................. 76 The National Library of Medicine: PubMed ...................................................... 79 Vocabulary Builder............................................................................................. 80

CHAPTER 5. PATENTS ON MUSCULAR DYSTROPHY ........................... 85

Overview............................................................................................................. 85 Patents on Muscular Dystrophy ........................................................................ 86 Patent Applications on Muscular Dystrophy .................................................. 103 Keeping Current ............................................................................................... 104 Vocabulary Builder........................................................................................... 104

CHAPTER 6. BOOKS ON MUSCULAR DYSTROPHY ............................. 107

Overview........................................................................................................... 107 Book Summaries: Federal Agencies .................................................................. 107 Book Summaries: Online Booksellers ............................................................... 108 The National Library of Medicine Book Index ................................................. 111 Chapters on Muscular Dystrophy.................................................................... 115 Directories......................................................................................................... 117 General Home References ................................................................................. 119 Vocabulary Builder........................................................................................... 120

CHAPTER 7. MULTIMEDIA ON MUSCULAR DYSTROPHY .................. 123

Overview........................................................................................................... 123 Video Recordings .............................................................................................. 123 Bibliography: Multimedia on Muscular Dystrophy ........................................ 124 Vocabulary Builder........................................................................................... 127

CHAPTER 8. PERIODICALS AND NEWS ON MUSCULAR DYSTROPHY 129

Overview........................................................................................................... 129 News Services & Press Releases ....................................................................... 129 Newsletters on Muscular Dystrophy ............................................................... 136 Academic Periodicals covering Muscular Dystrophy ...................................... 137 Vocabulary Builder........................................................................................... 139

CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES ................... 141

Overview........................................................................................................... 141 NIH Guidelines................................................................................................. 141 NIH Databases.................................................................................................. 142 Other Commercial Databases ........................................................................... 146 The Genome Project and Muscular Dystrophy................................................ 146 Specialized References....................................................................................... 151 Vocabulary Builder........................................................................................... 153

CHAPTER 10. DISSERTATIONS ON MUSCULAR DYSTROPHY ............ 155

Overview........................................................................................................... 155 Dissertations on Muscular Dystrophy............................................................. 155 Keeping Current ............................................................................................... 156 Vocabulary Builder........................................................................................... 157

PART III. APPENDICES .................................................. 159

Contents

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APPENDIX A. RESEARCHING YOUR MEDICATIONS.......................... 161

Overview........................................................................................................... 161 Your Medications: The Basics .......................................................................... 162 Learning More about Your Medications .......................................................... 164 Commercial Databases...................................................................................... 165 Contraindications and Interactions (Hidden Dangers) ................................... 166 A Final Warning .............................................................................................. 168 General References............................................................................................ 168 Vocabulary Builder........................................................................................... 169

APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ................... 171

Overview........................................................................................................... 171 What Is CAM? ................................................................................................. 171 What Are the Domains of Alternative Medicine?............................................ 172 Can Alternatives Affect My Treatment? ......................................................... 175 Finding CAM References on Muscular Dystrophy ......................................... 176 Additional Web Resources................................................................................ 183 General References............................................................................................ 188

APPENDIX C. RESEARCHING NUTRITION ......................................... 191

Overview........................................................................................................... 191 Food and Nutrition: General Principles........................................................... 192 Finding Studies on Muscular Dystrophy ........................................................ 196 Federal Resources on Nutrition........................................................................ 200 Additional Web Resources................................................................................ 201 Vocabulary Builder........................................................................................... 205

APPENDIX D. FINDING MEDICAL LIBRARIES.................................... 207

Overview........................................................................................................... 207 Preparation ....................................................................................................... 207 Finding a Local Medical Library ...................................................................... 208 Medical Libraries Open to the Public............................................................... 208

APPENDIX E. YOUR RIGHTS AND INSURANCE ................................. 215

Overview........................................................................................................... 215 Your Rights as a Patient................................................................................... 215 Patient Responsibilities .................................................................................... 219 Choosing an Insurance Plan............................................................................. 220 Medicare and Medicaid .................................................................................... 222 NORD’s Medication Assistance Programs ..................................................... 225 Additional Resources ........................................................................................ 226

ONLINE GLOSSARIES.................................................... 227 Online Dictionary Directories.......................................................................... 232

MUSCULAR DYSTROPHY GLOSSARY ..................... 233 General Dictionaries and Glossaries ................................................................ 247

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Contents

INDEX................................................................................... 249

Introduction

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INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don't know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, in March 2001 the National Institutes of Health issued the following warning: The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.3

Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2

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Muscular Dystrophy

Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor's offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The 2002 Official Patient’s Sourcebook on Muscular Dystrophy has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to muscular dystrophy, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on muscular dystrophy. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on muscular dystrophy should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on

Introduction

3

appropriate options is always up to the patient in consultation with their physician and healthcare providers.

Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching muscular dystrophy (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to muscular dystrophy. It also gives you sources of information that can help you find a doctor in your local area specializing in treating muscular dystrophy. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with muscular dystrophy. Part II moves on to advanced research dedicated to muscular dystrophy. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on muscular dystrophy. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with muscular dystrophy or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with muscular dystrophy. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with muscular dystrophy.

Scope While this sourcebook covers muscular dystrophy, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that muscular dystrophy is often considered a synonym or a condition closely related to the following: ·

Distal Muscular Dystrophy

·

Duchenne's Muscular Dystrophy

4

Muscular Dystrophy

·

Erb's Muscular Dystrophy

·

Facioscapulohumeral Disease

·

Fukuyama Syndrome

·

Gower's Syndrome

·

Inherited Myopathy

·

Landouzy-dejerine Disease

·

Landouzy-dejerine Dystrophy

·

Landouzy-déjèrine Dystrophy

·

Limb-girdle Muscular Dystrophy

·

Myotonic Muscular Dystrophy

·

Ocular Muscular Dystrophy

·

Oculopharyngeal Muscular Dystrophy

·

Pseudohypertrophic Muscular Dystrophy

·

Steinert's Disease

In addition to synonyms and related conditions, physicians may refer to muscular dystrophy using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world's illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for muscular dystrophy:4 ·

359 muscular dystrophies and other myopathies

·

359.0 congenital muscular dystrophy

·

359.1 hereditary progressive muscular dystrophy

· 359.2 myotonic dystrophy For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to muscular dystrophy. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.

4 This list is based on the official version of the World Health Organization's 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”

Introduction

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Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson's approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful. As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with muscular dystrophy will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with muscular dystrophy is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. Before beginning your search for information, it is important for you to realize that muscular dystrophy is considered a relatively uncommon condition. Because of this, far less research is conducted on muscular dystrophy compared to other health problems afflicting larger populations, like breast cancer or heart disease. Nevertheless, this sourcebook will prove useful for two reasons. First, if more information does become available on muscular dystrophy, the sources given in this book will be the most likely to report or make such information available. Second, some will find it important to know about patient support, symptom management, or diagnostic procedures that may be relevant to both muscular dystrophy and other conditions. By using the sources listed in the following chapters, selfdirected research can be conducted on broader topics that are related to muscular dystrophy but not readily uncovered using general Internet search engines (e.g. www.google.com or www.yahoo.com). In this way, we have

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Muscular Dystrophy

designed this sourcebook to complement these general search engines that can provide useful information and access to online patient support groups.5 While we focus on the more scientific aspects of muscular dystrophy, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors

For example, one can simply go to www.google.com, or other general search engines (e.g. www.yahoo.com, www.aol.com, http://www.msn.com/) and type in “muscular dystrophy support group” to find any active online support groups dedicated to muscular dystrophy.

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7

PART I: THE ESSENTIALS

ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on muscular dystrophy. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of muscular dystrophy to you or even given you a pamphlet or brochure describing muscular dystrophy. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.

Guidelines

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CHAPTER 1. THE ESSENTIALS ON MUSCULAR DYSTROPHY: GUIDELINES Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on muscular dystrophy. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on muscular dystrophy can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

The National Institutes of Health (NIH)6 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on muscular dystrophy. Originally founded in 1887, the NIH is one of the world's foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world's most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.

6

Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.

10 Muscular Dystrophy

There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with muscular dystrophy and associated conditions: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc. ) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines at http://www.nih.gov/niams/healthinfo/

Among those listed above, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is especially noteworthy. The mission of NIAMS, a part of the National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS that provides health information and information sources. The NIAMS provides the following guideline concerning muscular dystrophy.7

What Is Muscular Dystrophy (MD)?8 Muscular dystrophy (MD) refers to a group of genetic diseases characterized by progressive weakness and degeneration of the skeletal or voluntary muscles which control movement. The muscles of the heart and some other involuntary muscles are also affected in some forms of MD, and a few forms involve other organs as well. The major forms of MD include myotonic, Duchenne, Becker, limb-girdle, facioscapulohumeral, congenital, oculopharyngeal, distal and Emery-Dreifuss. Duchenne is the most common 7 This and other passages are adapted from the NIH and NIAMS (http://www.niams.nih.gov/hi/index.htm). “Adapted” signifies that the text is reproduced with attribution, with some or no editorial adjustments. 8 Adapted from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): http://www.ninds.nih.gov/health_and_medical/disorders/md.htm.

Guidelines 11

form of MD affecting children, and myotonic MD is the most common form affecting adults. MD can affect people of all ages. Although some forms first become apparent in infancy or childhood, others may not appear until middle age or later.

Is There Any Treatment? There is no specific treatment for any of the forms of MD. Physical therapy to prevent contractures (a condition in which shortened muscles around joints cause abnormal and sometimes painful positioning of the joints), orthoses (orthopedic appliances used for support) and corrective orthopedic surgery may be needed to improve the quality of life in some cases. The cardiac problems that occur with Emery-Dreifuss MD and myotonic MD may require a pacemaker. The myotonia (delayed relaxation of a muscle after a strong contraction) occurring in myotonic MD may be treated with medications such as phenytoin or quinine.

What Is the Prognosis? The prognosis of MD varies according to the type of MD and the progression of the disorder. Some cases may be mild and very slowly progressive, with normal lifespan, while other cases may have more marked progression of muscle weakness, functional disability and loss of ambulation. Life expectancy may depend on the degree of progression and late respiratory deficit. In Duchenne MD, death usually occurs in the late teens to early 20s.

What Research Is Being Done? The NINDS supports a broad program of research on MD. The goals of these studies are to increase understanding of MD and its cause(s), develop better therapies, and, ultimately, find ways to prevent and cure the disorder.


Organizations Facioscapulohumeral Dystrophy (FSHD) Society 3 Westwood Road Lexington, MA 02420 [email protected] http://www.fshsociety.org Tel: 781-860-0501 Fax: 781-860-0599 Muscular Dystrophy Association 3300 East Sunrise Drive Tucson, AZ 85718-3208 [email protected] http://www.mdausa.org/ Tel: 520-529-2000 800-572-1717 Fax: 520-529-5300 Muscular Dystrophy Family Foundation 2330 North Meridien Street Indianapolis, IN 46208 [email protected] http://www.mdff.org Tel: 317-923-6333 800-544-1213 Fax: 317-923-6334 Parent Project for Muscular Dystrophy Research 1012 North University Blvd. Middletown, OH 45042 [email protected] http://www.parentprojectmd.org Tel: 413-424-0696 800-714-KIDS (5437) Fax: 513-425-9907

More Guideline Sources The guideline above on muscular dystrophy is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to muscular dystrophy. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with

Guidelines 13

muscular dystrophy. Due to space limitations these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.

Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.

The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on muscular dystrophy and related conditions. One of the advantages of CHID over other sources is that it offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·

FSHD [Facioscapulohumeral Muscular Dystrophy] Source: Lexington, MA: FSH Society, Inc. 1997. 12 p. Contact: Available from FSH Society, Inc. Administrative Office, 3 Westwood Road, Lexington, MA 02420. (781) 860-0501. Fax (781) 8600599. Web Site: fshsociety.org. PRICE: Single copy free.


Summary: This brochure for people with facioscapulohumeral muscular dystrophy (FSHD) uses a question and answer format to provide information on the cause, symptoms, prognosis, and treatment of this autosomal dominant inherited disease. The estimated occurrence of FSHD is one in 20,000. Most people who have FSHD inherited a chromosome 4 genetic mutation from a parent with the disease. FSHD is characterized by progressive weakening and loss of skeletal muscle. Symptoms are usually first seen in the face, shoulders, and upper arms. Muscles in the neck, torso, and lower limbs eventually weaken also. People with the disease typically begin to notice muscle weakness during adolescence, and a physician can usually recognize and diagnose the disease by the age of 20. An infantile form of FSHD may occur in rare instances. Prognosis is variable, and there is no treatment or cure for FSHD, physical, occupational, and nutrition therapy may be beneficial. Surgery to attach the scapulae to the back may be performed in some cases. The brochure also provides information on the FSH Society. 1 figure. ·

Facts About Friedreich's Ataxia Source: Tucson, AZ: Muscular Dystrophy Association. 1999. 16 p. Contact: Available from Muscular Dystrophy Association. Publications Department, 3300 East Sunrise Drive, Tucson, AZ 85718. (800) 572-1717 or (520) 529-2000. Website: www.mdausa.org. PRICE: Single copy free. Summary: This brochure describes Friedreich's ataxia (FRDA), an inherited progressive disorder of the nervous system that affects balance, coordination, movement, and sensation. Ataxia refers to a loss of coordination and is usually the earliest and most prominent characteristic of the disease. Increasing impairment of balance and movement eventually lead to the loss of the ability to walk; speech and swallowing difficulties may occur as well. The brochure is written in a question and answer format and covers incidence, heredity, recessive inheritance, symptoms, treatment options, disease progression, speech and swallowing problems associated with FRDA, how FRDA affects the heart, genetic testing, and the role of the Muscular Dystrophy Association (MDA). The brochure concludes with a brief description of the purpose and programs of the MDA. 7 figures.

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Augmentative Communication: Consumers Source: Rockville, MD: American Speech-Language-Hearing Association (ASHA). 199x. 36 p.

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Contact: Available from American Speech-Language-Hearing Association (ASHA). Product Sales, 10801 Rockville Pike, Rockville, MD 20852. (888) 498-6699. TTY (301) 897-0157. Website: www.asha.org. PRICE: $1.50 per booklet. Item Number 0210251. Summary: This consumer information booklet describes the use of augmentative communication for people who can hear but have little or no usable speech. Such severe communication disabilities can result from severe language delay, cerebral palsy, mental retardation, autism, traumatic brain injury (TBI), or stroke. In addition, a variety of specific neuromuscular disorders, such as amyotrophic lateral sclerosis (ALS), dystonia, Huntington's disease, multiple sclerosis, and muscular dystrophy can also cause severe speech problems. Augmentative communication is defined as any method other than speech, to send a message from one person to another. Techniques of augmentative communication range from specialized gestures and sign language to communication aids such as sign boards to highly specialized computerbased techniques. The booklet emphasizes the implementation of an effective augmentative communication system, regardless of level of sophistication, requires a detailed multidisciplinary assessment, training for the user(s), and regular re-evaluation. The booklet outlines the roles of members of the patient care team, including the speech language pathologist, the occupational therapist, the physical therapist, physicians, the educator, social worker, psychologist, rehabilitation engineer, computer programmer, vocational counselor, audiologist, orthotist, and manufacturers or distributors of communication devices. The author encourages readers to become active partners in their own care or the care of their children with communication disorders. The booklet includes a resource list of professional and consumer groups concerned with augmentative communication. An appendix provides a glossary of some of the terms used in augmentative communication. The booklet is illustrated with black and white photographs.

The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “muscular dystrophy” or synonyms. The following was recently posted: ·

ACC/AHA guidelines for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of


Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Pacemaker Implantation). Source: American College of Cardiology/American Heart Association.; 1998 April (reviewed 2000); 34 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0495&sSearch_string=muscular+dystrophy ·

Clinical practice guidelines for the use of chemotherapy and radiotherapy protectants. Source: American Society of Clinical Oncology.; 1999 October; 23 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 1376&sSearch_string=muscular+dystrophy

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Evaluation anesthesia.

and

preparation

of

pediatric

patients

undergoing

Source: American Academy of Pediatrics.; 1996 September; 12 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0999&sSearch_string=muscular+dystrophy ·

Practice advisory on the treatment of amyotrophic lateral sclerosis with riluzole. Source: American Academy of Neurology.; 1997; 3 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0652&sSearch_string=muscular+dystrophy

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Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Source: American Academy of Neurology.; 2000 July; 9 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2052&sSearch_string=muscular+dystrophy Healthfinder™

Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which offers links to hundreds of other sites that

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contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·

FAQ - About Loving Paws Dogs Summary: Loving Paws Dogs are service dogs trained for disabled children (specifically muscular dystrophy, cerebral palsy and spina bifida) up to aged 18. This information answers questions about the program. Source: Loving Paws Assistance Dogs http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=4239

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Muscular Dystrophy Summary: Muscular dystrophy (MD) refers to a group of genetic diseases characterized by progressive weakness and degeneration of the skeletal or voluntary muscles which control movement. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=749

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Treating Scoliosis in Muscular Dystrophy Summary: Written especially for children with muscular dystrophy, this booklet provides information concerning scoliosis treatments. Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=4097

The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to muscular dystrophy. The drawbacks of this approach are


that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites that often link to government sites are available to the public. These can also point you in the direction of essential information. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

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drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html

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Family Village: http://www.familyvillage.wisc.edu/specific.htm

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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

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Med Help International: http://www.medhelp.org/HealthTopics/A.html

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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

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WebMDÒHealth: http://my.webmd.com/health_topics

Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH]

Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH]

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Ataxia: Failure of muscular coordination; irregularity of muscular action. [EU]

Cardiac: Pertaining to the heart. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Electrodiagnosis: Diagnosis of disease states by recording the spontaneous electrical activity of tissues or organs or by the response to stimulation of electrically excitable tissue. [NIH] Gestures: Movement of a part of the body for the purpose of communication. [NIH] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Infantile: Pertaining to an infant or to infancy. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myopathy: Any disease of a muscle. [EU] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU]


Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Radiotherapy: The treatment of disease by ionizing radiation. [EU] Respiratory: Pertaining to respiration. [EU] Riluzole: A glutamate antagonist that has reported anticonvulsant activity. It has been shown to prolong the survival of patients with amyotrophic lateral sclerosis and has been approved in the United States to treat patients with ALS. [NIH] Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU]

Seeking Guidance 21

CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with muscular dystrophy. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.9 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with muscular dystrophy. The chapter ends with a discussion on how to find a doctor that is right for you.

Associations and Muscular Dystrophy As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.10 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your condition can all Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 10 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 9


influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·

Challenge Air For Kids and Friends Address: Challenge Air For Kids and Friends Love Field North Concourse, 8008 Cedar Springs Road, Suite N106 LB24, Dallas, TX 75235 Telephone: (214) 351-3353 Toll-free: (800) 714-5437 Fax: (214) 351-4565 Email: [email protected] Web Site: http://www.challengeair.co Background: Challenge Air for Kids and Friends is a national nonprofit organization dedicated to providing motivational, occupational, recreational, and educational therapy to disabled, disadvantaged, and seriously ill children through the experience of flight with a disabled pilot free of charge. Challenge Air was established in 1993 by a pilot who lost the use of his legs when his plane crashed while returning from a combat mission over Vietnam. The purpose of the flights is to provide enjoyable experiences and to demonstrate that the human spirit can prevail over any physical or mental obstacle. Challenge Air organizes day long events that allow groups of children to enjoy motivational flights, food, and other fun. Events have include handicapped athletic groups, therapy programs, social service organizations, and more. A typical Challenge Air fly day serves more than 150 children and their families. Each program is underwritten by individual, corporate, and philanthropic donations. Challenge Air has flown over 4,000 children in 15 states as well as Canada. Challenge Air has several materials available including brochures, pamphlets, videos, and a newsletter. Challenge Air also has a web site at http://www.challengeair.com. Relevant area(s) of interest: Muscular Dystrophy

Seeking Guidance 23

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Citizens For Independence In Living And Breathing Telephone: (416) 227-0623 Toll-free: (800) 714-5437 Fax: (416) 277-062 Background: The Citizens For Independence In Living and Breathing (CILB) is a not-for-profit organization dedicated to promoting choice, control, and independence through education and information for both current and prospective ventilator users with neuromuscular disorders. CILB was established in 1988, when community action funding enabled the Canadian Paraplegic Association to investigate the needs of severely disabled individuals including ventilator users. CILB assists the community by providing information concerning the choice of independent living options available to individuals who are capable of directing their own services; publishing and disseminating information about living with a ventilator and alternative ventilation techniques; providing information about available community services, attendant services, health care, education, employment, and recreation; providing information regarding funding for the hiring and training of attendants; and assisting in the development of support networks for users, families, and others who require assistance. CILB consists of 65 active members who participate in various advisory committees and groups such as Ontario Ministries including Health, Community and Social Services, Housing, and Education and Citizenship; the Canadian Standards Association; and District Health Councils. Educational materials include pamphlets, CILB conference session tapes, and videotapes.

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Disabled Sports USA Address: Disabled Sports USA 451 Hungerford Drive, Suite 100, Rockville, MD 20850 Telephone: (301) 217-0960 Toll-free: 1 800 656 632 Fax: (301) 217-0968 Email: [email protected] Web Site: http://www.dsusa.org/~dsusa/dsusa.htm Background: Disabled Sports USA (DS/USA) is a not-for-profit organization dedicated to ensuring that disabled people have access to sports, recreation, and physical education programs from preschool through college to elite sports levels. Established in 1967 by disabled Vietnam veterans, DS/USA serves people with physical disabilities that restrict mobility, including amputations, weakness or paralysis of both legs (paraplegia), paralysis of all four limbs (quadriplegia), cerebral palsy, head injury, multiple sclerosis, muscular dystrophy, spina bifida,


stroke, and visual impairment. DS/USA consists of more than 60,000 members and 80 chapters around the United States. Educational materials include a general information packet, a newsletter entitled 'Disabled Sports USA Update,' and a sports magazine entitled 'Challenge.' Program activities include sporting activities and events, patient education (e.g., workshops), and patient networking. DS/USA maintains a web site at http://www.dsusa.org/~dsusa/dsusa.html. ·

European Alliance of Muscular Dystrophy Associations Address: European Alliance of Muscular Dystrophy Associations 7-11 Prescott Place, London, SW4 6BS, United Kingdom Telephone: 44 171 720 8055 Toll-free: 1 800 656 632 Fax: 44 171 498 8963 Email: [email protected] Web Site: http://www.sonnet.co.uk/eamda Background: The European Alliance of Muscular Dystrophy Associations (EAMDA) is a nonprofit organization that was established in 1971. The organization consists of delegates from its over 30 member associations and primarily serves as an information network, providing advice about neuromuscular conditions and offering information, support, and resources to families, caregivers, and professionals throughout Europe. Muscular dystrophy refers to a group of genetic disorders characterized by progressive degeneration of muscle fibers, resulting in associated weakness, disability, and deformity. The different forms of muscular dystrophy may be categorized based upon age at onset, specific muscle groups affected, rate of disease progression, and mode of inheritance. Forms of muscular dystrophy include Becker muscular dystrophy, Duchenne muscular dystrophy, and ocular myopathies. The EAMDA includes a Youth Organization, known as the EYO, that is made up of delegates who represent the young people in their own national associations. The EYO is committed to providing assistance and support for young people with muscular dystrophy; promoting networking among affected youths, encouraging the exchange of information and mutual support; and providing assistance to the National Youth Organizations concerning the different aspects of these disorders, such as quality of life issues, self image, and medical intervention. The EAMDA also offers a variety of educational materials including fact sheets on the different forms of muscular dystrophy, a regular newsletter, and several additional publications. The EAMDA's web site on the Internet provides information on the Alliance and its Youth Organization; access to MD fact sheets, the EAMDA newsletter, and a glossary of MD-related terms;

Seeking Guidance 25

contact information for neuromuscular disorder support groups; and links to additional sources of information and support. Relevant area(s) of interest: Muscular Dystrophy ·

Facio-Scapulo-Humeral Society, Inc Address: Facio-Scapulo-Humeral Society, Inc. 3 Westwood Road, Lexington, MA 02420 Telephone: (781) 860-0501 Toll-free: (800) 433-5255 Fax: (781) 860-0599 Email: [email protected] Web Site: http://www.fshsociety.or Background: Facio-Scapulo-Humeral Society, Inc. (FSH Society) is a voluntary not- for-profit organization created to address issues and needs specifically related to Facio-Scapulo-Humeral Muscular Dystrophy (FSHD), a rare inherited neuromuscular disorder. Established in 1989, the Facio-Scapulo-Humeral Society is dedicated to encouraging and promoting ongoing scientific and clinical research and development into the nature of Facio-Scapulo-Humeral Syndrome through solicitation of grants and contributions from private foundations, the pharmaceutical industry, and others. The Society also seeks to develop educational programs aimed at the medical community, government bodies, and the public. The Society accumulates and disseminates timely information about FSHD and actively cooperates with related organizations to foster communication among all interested parties. In addition, Facio-ScapuloHumeral Society promotes professional education; provides appropriate referrals including to support groups; and promotes patient advocacy and legislation beneficial to individuals with FSHD. The Society offers a variety of educational and support materials including brochures, fact sheets, and a newsletter. The FSH Society provies grants for research on FSHD.

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March of Dimes Birth Defects Foundation Address: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue, White Plains, NY 10605 Telephone: (914) 428-7100 Toll-free: (888) 663-4637 Fax: (914) 997-4763 Email: [email protected] Web Site: http://www.modimes.or


Background: The March of Dimes Birth Defects Foundation is a national not-forprofit organization that was established in 1938. The mission of the Foundation is to improve the health of babies by preventing birth defects and infant mortality. Through the Campaign for Healthier Babies, the March of Dimes funds programs of research, community services, education, and advocacy. Educational programs that seek to prevent birth defects are important to the Foundation and to that end it produces a wide variety of printed informational materials and videos. The March of Dimes public health educational materials provide information encouraging health- enhancing behaviors that lead to a healthy pregnancy and a healthy baby. ·

Muscular Dystrophy Association Address: Telephone: (520) 529-2000 Toll-free: (800) 572-1717 Fax: (520) 529-5300 Email: [email protected] Web Site: http://www.mdausa.or Background: Established in 1950, the Muscular Dystrophy Association (MDA) is a non-profit, voluntary health agency dedicated to providing comprehensive medical services to individuals affected by neuromuscular diseases. MDA provides these services at 240 hospitalaffiliated clinics across the United States. The Association s worldwide research program, which funds approximately 400 individual scientific investigations each year, represents the largest single initiative to advance current knowledge of neuromuscular diseases and to find cures and treatments for this group of diseases. At facilities in MDA's hospitalaffiliated clinics, affected individuals receive diagnosis and follow-up care from specialists in neuromuscular diseases. In addition to its medical services and research programs, MDA conducts educational programs for the public and for medical professionals. The Association publishes and distributes a wide variety of print materials. MDA also sponsors scientific symposia as well as other meetings of specialists in the field of neuromuscular disorders. Relevant area(s) of interest: Muscular Dystrophy

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Muscular Dystrophy Association (Australia) Address: Muscular Dystrophy Association (Australia) GPO Box 9932, Melbourne, 3001, Australia Telephone: 61 3 9370 0477 Toll-free: 1 800 656 632

Seeking Guidance 27

Fax: 61 3 9370 0393 Email: [email protected] Web Site: http://www.mda.org.a Background: The Muscular Dystrophy Association (MDA) is a not-forprofit organization in Australia that was founded in the early 1970s by a group of people affected by muscular dystrophy (MD). Muscular dystrophy refers to a group of genetic disorders characterized by progressive degeneration of muscle fibers, resulting in associated weakness, disability, and deformity. The different forms of muscular dystrophy may be categorized based upon age at onset, specific muscle groups affected, rate of disease progression, and mode of inheritance. The Muscular Dystrophy Association is committed to improving the quality of life of individuals with muscular dystrophy and other neuromuscular diseases. To fulfill its mission and objectives, the Association provides a variety of educational materials, conducts MDA camps for children and adults with neuromuscular disorders, and promotes and supports research. The Association's materials include information sheets on different forms of muscular dystrophy, parents guides, glossaries, and materials discussing the various aspects of these disorders. The Association also maintains a web site on the Internet that provides understandable information on muscular dystrophy, a FAQ ('frequently asked questions') area, a guestbook area for online visitors, and links to additional sources of information and support. In 1985, the Association established the Muscular Dystrophy Research Foundation to help ensure sufficient funding to accelerate research and to provide funds required for treatment programs. The MDA, in association with St. Vincents Hospital and the Department of Medicine, Melbourne University, is also affiliated with the Melbourne Neuromuscular Research Centre, and sponsors scientific research seminars and conferences. Relevant area(s) of interest: Muscular Dystrophy ·

Muscular Dystrophy Association of Canada Address: Telephone: 416-488-2699 Toll-free: (800) 567-2873 EFax: 416-488-7523 Web Site: http://www.mdac.c Background: The Muscular Dystrophy Association of Canada (MDAC) is not-for-profit voluntary organization dedicated to eliminating neuromuscular disorders and alleviating the associated symptoms. 'Neuromuscular disorders' are a group of diseases affecting the body s


ability to move due to an underlying neurological disease. Whether the problem originates within the motor nerve cell, the nerve, or the muscle, the most commonly experienced symptoms are varying degrees of progressive muscle weakness and wasting. There are over 40 nerve and muscle disorders covered under the umbrella of the Muscular Dystrophy Association of Canada. Founded in 1954, the Association s three main goals are funding research that will ultimately result in discovering the causes, treatments, and cures for muscular dystrophy and other neuromuscular disorders; providing support services that assist individuals and families affected by neuromuscular disorders; and providing information to affected individuals, their families, health care professionals, educators, and the general public as to the nature and management of neuromuscular disorders. Services provided by MDAC include the dissemination of information, advocacy, referrals, travel assistance, and some financial assistance with mobility equipment. MDAC also houses donated equipment for use by clients upon request. Informational brochures include 'What Is Spinal Muscular Atrophy?,' 'What Is Myotonic Dystrophy?,' and 'What Is Muscular Dystrophy?'. MDAC also publishes a news magazine entitled 'CONNECTIONS' that features information and articles on various neuromuscular disorders and on related topics such as research, genetics, parenting, and coping with a disability. Additionally, the organization provides advocacy services in resolving individual or community problems. Such issues might involve education, employment, or transportation. Relevant area(s) of interest: Muscular Dystrophy ·

Muscular Dystrophy Group of Great Britain and Northern Ireland Address: Muscular Dystrophy Group of Great Britain and Northern Ireland 7-11 Prescott Place, London, SW4 6BS, United Kingdom Telephone: 0171 720 8055 Toll-free: 1 800 656 632 Fax: 0171 498 0670 Email: [email protected] Web Site: http://www.sonnet.co.uk/muscular-dystroph Background: The Muscular Dystrophy Group of Great Britain and Northern Ireland (MDG) is a voluntary research organization dedicated to identifying the causes of muscular dystrophy and allied conditions in order to develop treatments that will alleviate symptoms while working to discover a cure. Muscular Dystrophy (MD) is a group of rare inherited muscle wasting diseases. In some forms of MD, muscles of the hips and shoulders are weakened, walking abnormalities (ataxia) develop, and mild mental retardation may be present. MDG was established in 1959

Seeking Guidance 29

and is affiliated with two other organizations, the European Alliance of MDA and the World Alliance of MDA. The MDG currently provides funding for seven Muscle Centers that are designed to provide comprehensive medical care to individuals with neuromuscular conditions, and to provide researchers within and between the Centers with medical data and samples that will assist research. There are two types of MDG grants to centers, a Research Servicing Grant which supports costs such as equipment servicing, specialist technicians, secretarial staff, etc. and a Medical Services Grant which provides computing facilities and secretarial staff. Educational materials include an annual review covering different areas of concern for people affected by Muscular Dystrophy. MDG can be reached on the world wide web at http://WWW.sonnet.co.uk/muscular-dystrophy. Relevant area(s) of interest: Muscular Dystrophy ·

Muscular Dystrophy Ireland Address: Muscular Dystrophy Ireland Carmichael House, North Brunswick Street, Dublin 7, , Ireland Telephone: 353 1 8721501 Toll-free: (800) 714-5437 Fax: 353 1 8724482 Email: [email protected] Web Site: http://www.mdi.ie Background: Muscular Dystrophy Ireland (MDI) is a national voluntary nonprofit organization with a membership of approximately 500 individuals and families throughout Ireland. The organization's primary objective is to provide support to people with muscular dystrophy and their families through the provision of a range of services, including counseling, respite services, holidays, youth activities, and independent living and training opportunities. Muscular dystrophy is a collective term referring to a variety of genetic neuromuscular disorders characterized by progressive degeneration and weakening of muscles. The different forms of muscular dystrophy may be categorized based upon age at onset, specific muscle groups affected, rate of disease progression, and mode of inheritance. Muscular Dystrophy Ireland was founded in 1972 and currently has a head office as well as two divisional offices. In addition to providing supportive services, the MDI is committed to promoting and supporting research, conducting annual general meetings, organizing special youth activities for its younger members, and offering a variety of educational materials including the 'MDI Magazine.' Muscular Dystrophy Ireland also maintains a web site on the Internet that discusses the organization's mission, objectives, and services; offers a


guestbook area for online visitors; and provides linkage to additional sources of information and support. Relevant area(s) of interest: Muscular Dystrophy ·

Parent Project for Muscular Dystrophy Research Address: Telephone: (513) 424-7452. Toll-free: (800) 714-543 Fax: (513) 425-9907. Background: The Parent Project for Muscular Dystrophy Research is a not-for-profit national health organization dedicated to funding ongoing medical research to find a cure for Duchenne Muscular Dystrophy. Duchenne Muscular Dystrophy is a chronic, progressive, inherited form of muscular dystrophy usually beginning in early childhood; it is characterized by enlargement of muscles, weakness in the pelvis and shoulders, muscular atrophy, and additional symptoms. Established in 1994, the organization's scientific review board is in place to channel funding to those areas currently lacking in research funding. The Parent Project provides current information on Duchenne Muscular Dystrophy and related disorders such as Becker Muscular Dystrophy through brochures and audio-visual materials. Relevant area(s) of interest: Muscular Dystrophy

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Parent Project for Muscular Dystrophy Research, Inc Address: Parent Project for Muscular Dystrophy Research, Inc. 125 Marymont Court, Middletown, OH 45042 Telephone: (513) 424-7452 Toll-free: (800) 714-5437 Fax: (513) 425-9907 Email: [email protected] Web Site: http://www.parentdmd.or Background: The Parent Project for Muscular Dystrophy Research, Inc. (formerly the Parent Project for Duchenne Muscular Dystrophy) is a notfor-profit national health organization dedicated to funding ongoing medical research to find a cure for Duchenne Muscular Dystrophy. Duchenne Muscular Dystrophy is a chronic, progressive, inherited form of muscular dystrophy usually beginning in early childhood; it is characterized by enlargement of muscles, weakness in the pelvis and shoulders, muscular atrophy, and additional symptoms. Established in 1994, the organization has a scientific review board in place to channel funding to those areas currently lacking in research funding. The Parent

Seeking Guidance 31

Project provides current information on Duchenne Muscular Dystrophy and related disorders such as Becker Muscular Dystrophy through brochures and audio-visual materials. Relevant area(s) of interest: Muscular Dystrophy ·

Scapuloperoneal Disease Association Address: Scapuloperoneal Disease Association 610 Navesink Avenue, Ocean Gate, NJ 08740 Telephone: (908) 269-0357 Toll-free: (800) 826-0826 Fax: (908) 269- 035 Background: The Scapuloperoneal Disease Association (SPDA) is an international self-help and research organization dedicated to providing information, assistance, and support to individuals and family members affected by Scapuloperoneal Muscular Dystrophy. Scapuloperoneal Muscular Dystrophy, a rare inherited muscular dystrophy that may become apparent early in life, is characterized by slowly progressive muscle weakness of the upper arms and shoulder blade area (scapula) as well as certain leg muscle groups below the knee (peroneal). Established in 1994, the SPDA provides networking services that enable affected individuals and family members to exchange information, support and resources; promotes basic and clinical research development; fosters communication among related organizations; serves to represent individuals and family members affected by Scapuloperoneal Muscular Dystrophy; and accumulates and disseminates information and materials concerning this disorder.

·

Shriners Hospitals for Children Address: Shriners Hospitals for Children P.O. Box 31356, Tampa, FL 33613-3356 Telephone: (813) 281-0300 Toll-free: (800) 237-5055 Fax: (813) 281-8496 Web Site: http://www.shrinershq.or Background: The Shriners Hospital for Children and the Shriners Burn Institutes are a network of pediatric hospitals that provide no-cost medical care to children with orthopedic problems or burn injuries. Shriners Hospital conducts research on orthopedic treatment and burn care and trains healthcare professionals in the treatment of orthopedic disabilities and burn injuries. Established in 1922, the hospitals are substantially funded through the Shriners Hospital for Children


endowment fund. The hospitals treat children with a variety of diseases including (but not limited to) scoliosis, osteogenesis imperfecta, Legg Calve Perthes, and others. Burns and spinal injuries are also treated. Shriners Hospital consists of 23 chapters and offers educational materials such as 'Between Us' magazine, '20 Questions,' and 'The Story of Shriners Hospitals.' In addition, the organization assists in training physicians and other medical professionals in the treatment of orthopedic disabilities and burn injuries. The Shriners also operate a World Wide Web site at http://www.shrinershq.org. Relevant area(s) of interest: Muscular Dystrophy, Scoliosis ·

Society for Muscular Dystrophy Information International Address: Society for Muscular Dystrophy Information International P.O. Box 479, Bridgewater, Nova Scotia, B4V 2X6, Canada Telephone: (902) 685-3961 Toll-free: (800) 714-5437 Fax: (902) 685-3962 Email: [email protected] Web Site: Non Background: The Society for Muscular Dystrophy Information International (SMDI) is a not-for-profit registered Canadian charity dedicated to assisting people in helping themselves by reducing the national and international isolation of individuals and organizations concerned with neuromuscular disorders/disabilities (e.g., muscular dystrophy and over 50 allied disorders). In general, 'neuromuscular disorder' is a term used to describe a group of over 50 diseases affecting the body's motor neurons (nerves and muscles). Symptoms may include varying degrees of progressive muscle weakness and loss of muscle mass (wasting). SMDI was established in 1983 to provide a non-technical information link for individuals with neuromuscular disorders and for organizations around the world; to link people with other people and organizations concerned with their disorder; to share information to assist people in helping themselves; and to create increased public awareness of this group of disorders. The Society publishes two biannual newsletters entitled 'SMDI International Newsletter,' a publication for those concerned with muscular dystrophy or the allied disorders and 'Access - Able Information,' a quarterly disability information resource publication. In addition to educational materials, brochures and referrals are available. Relevant area(s) of interest: Muscular Dystrophy

Seeking Guidance 33

Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations.

The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about muscular dystrophy. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “muscular dystrophy” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “muscular dystrophy”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” By making these selections and typing in “muscular dystrophy” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with muscular dystrophy. You should check back periodically with this database since it is updated every 3 months.


The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “muscular dystrophy” (or a synonym) in the search box.

Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective. The following Internet sites may be of particular interest: ·

The Muscular Dystrophy Adult Support Group www.onyx.org/mdasg.htm

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FSH-Muscular Dystrophy Support Group www.fsh-group.org

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Muscular Dystrophy Association Support Group www.ggc.org/mdasup.html

Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with muscular dystrophy must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:11 ·

If you are in a managed care plan, check the plan's list of doctors first.

11

This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

Seeking Guidance 35

·

Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.

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Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.

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Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.

Additional steps you can take to locate doctors include the following: ·

Check with the associations listed earlier in this chapter.

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Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.

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The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at 12 http://www.abms.org/newsearch.asp. You can also contact the ABMS by phone at 1-866-ASK-ABMS.

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You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA's Web site: http://www.amaassn.org/aps/amahg.htm.

If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.

While board certification is a good measure of a doctor's knowledge, it is possible to receive quality care from doctors who are not board certified. 12


Selecting Your Doctor13 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·

Give me a chance to ask questions about muscular dystrophy?

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Really listen to my questions?

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Answer in terms I understood?

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Show respect for me?

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Ask me questions?

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Make me feel comfortable?

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Address the health problem(s) I came with?

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Ask me my preferences about different kinds of treatments for muscular dystrophy?

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Spend enough time with me?

Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.

Working with Your Doctor14 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·

You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.

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It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.

13 This

section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 14 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.

Seeking Guidance 37

·

Bring a “health history” list with you (and keep it up to date).

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Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.

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Tell your doctor about any natural or alternative medicines you are taking.

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Bring other medical information, such as x-ray films, test results, and medical records.

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Ask questions. If you don't, your doctor will assume that you understood everything that was said.

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Write down your questions before your visit. List the most important ones first to make sure that they are addressed.

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Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.

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Ask your doctor to draw pictures if you think that this would help you understand.

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Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.

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Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.

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Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.

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After leaving the doctor's office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.

By following these steps, you will enhance the relationship you will have with your physician.


Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:15 ·

Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html

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Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html

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Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html

Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Atrophy: A wasting away; a diminution in the size of a cell, tissue, organ, or part. [EU] Blindness: The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Hyperphagia: Ingestion of a greater than optimal quantity of food. [NIH] Hypogonadism: A condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [EU] You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.

15

Seeking Guidance 39

Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Nasal: Pertaining to the nose. [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Oral: Pertaining to the mouth, taken through or applied in the mouth, as an oral medication or an oral thermometer. [EU] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Paralysis: Loss or impairment of motor function in a part due to lesion of the neural or muscular mechanism; also by analogy, impairment of sensory function (sensory paralysis). In addition to the types named below, paralysis is further distinguished as traumatic, syphilitic, toxic, etc., according to its cause; or as obturator, ulnar, etc., according to the nerve part, or muscle specially affected. [EU] Paraplegia: Paralysis of the legs and lower part of the body. [EU] Quadriplegia: Severe or complete loss of motor function in all four limbs which may result from brain diseases; spinal cord diseases; peripheral nervous system diseases; neuromuscular diseases; or rarely muscular diseases. The locked-in syndrome is characterized by quadriplegia in combination with cranial muscle paralysis. Consciousness is spared and the only retained voluntary motor activity may be limited eye movements. This condition is usually caused by a lesion in the upper brain stem which injures the descending cortico-spinal and cortico-bulbar tracts. [NIH] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Ventilation: 1. in respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. in psychiatry, verbalization of one's emotional problems. [EU]

Clinical Trials 41

CHAPTER 3. CLINICAL TRIALS AND MUSCULAR DYSTROPHY Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning muscular dystrophy. What Is a Clinical Trial?16 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for muscular dystrophy is to try it on patients in a clinical trial.

What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·

Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.

The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.

16


·

Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on muscular dystrophy.

·

Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for muscular dystrophy compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment.

How Is a Clinical Trial Conducted? Various organizations support clinical trials at medical centers, hospitals, universities, and doctors' offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on muscular dystrophy carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on muscular dystrophy. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This treatment, like a placebo, has no effect on muscular dystrophy and does not harm patients. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is

43

about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how muscular dystrophy develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for muscular dystrophy. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial's investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients


who continue to return for follow-up examinations can provide this important long-term information.

Recent Trials on Muscular Dystrophy The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to muscular dystrophy.17 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·

A multicenter randomized placebo-controlled double-blind study to assess efficacy and safety of glutamine and creatine monohydrate in Duchenne muscular dystrophy (DMD) Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Children's National Medical Center Purpose - Excerpt: To establish a collaborative group of clinical trial centers, with standardized equipment and protocols, able to conduct both drug and gene therapy trials in DMD. To evaluate the therapeutic effect of glutamine and creatine monohydrate on muscle strength in children with DMD. To validate the use of QMT (quantitative muscle strength testing) and gait analysis in children with DMD as reliable tools to quantify muscle strength, monitor disease progression and assess therapeutic response. Phase(s): Phase III Study Type: Interventional Contact(s): Missouri; Washington University School of Medicine, St. Louis, Missouri, 63110, United States; Recruiting; Alan Pestronk, M.D. 314-362-6981 [email protected]; Alan Pestronk, M.D., Principal Investigator

17

These are listed at www.ClinicalTrials.gov.

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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00018109 ·

An open-label pilot study of Coenzyme Q10 in steroid-treated Duchenne muscular dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the safety and efficacy of the nutritional supplement Coenzyme Q10 when added to steroids as a treatment for Duchenne muscular dystrophy (DMD). Boys with DMD who are enrolled in this study will should be on a stable dose of steroids for at least six months, and will remain on their usual dose throughout the study. They will complete two screening visits within a one-week period, and if enrolled will then have their strength tested monthly for three months before beginning therapy with Coenzyme Q10. Once Coenzyme Q10 therapy is started, participants will have their strength tested monthly for six months. Following the six month treatment period, participants will be given the option to remain on Coenzyme Q10 until the study is completed. Phase(s): Phase II Study Type: Interventional Contact(s): Erik K Henricson, MPH 202-884-3813 EHenricson@ cnmcresearch.org Diana M Escolar, MD 202-884-6080 DEscolar@ cnmcresearch.org; District of Columbia; Children's National Medical Center, Washington, District of Columbia, 20010, United States; Recruiting; Erik K Henricson, MPH 202-884-3813 EHenricson@ cnmcresearch.org; Diana M Escolar, MD, Principal Investigator Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00033189

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Clinical trial of creatine in amyotrophic lateral sclerosis [ALS] Condition(s): Amyotrophic Lateral Sclerosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Muscular Dystrophy Association Purpose - Excerpt: The purpose of this study is to evaluate the safety and effectiveness of creatine treatment in amyotrophic lateral sclerosis (ALS). There is currently no known effective treatment for ALS. It is known that nerve cells die in the brains and spinal cords of patients with ALS but the cause of the cell death is unknown. It has been shown that there is


overactive nerve activity due to increased levels of a chemical called glutamate and that there is abnormal cellular metabolism along with increased production of substance called "free radicals." Improving cellular metabolism and readjusting the activity of glutamate in the brain may be beneficial to ALS patients. Creatine is a naturally occurring compound, which improves energy metabolism in cells. Creatine has been given to patients with energy metabolism defects in their muscles, and to athletes. Creatine improves survival in a mouse model of ALS. Three human subjects with ALS have received creatine for up to six months without any side effects. Overall, creatine has been well tolerated and safe. Phase(s): Phase II Study Type: Interventional Contact(s): Alan Pestronk, M.D. 1-314-362-6981 [email protected]; [email protected]; Missouri; Washington University, St. Louis, Missouri, 63110, United States; Recruiting; Alan Pestronk, M.D. 314-362-6981 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005674 ·

Creatine and Glutamine in Steroid-Naive Duchenne Muscular Dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the effectiveness of glutamine and creatine as a possible therapy for DMD. Boys with DMD who are enrolled in this trial will be randomly chosen to receive creatine monohydrate or glutamine or an inactive placebo orally for six months. Once a month during the six-month treatment period, the study participants will have their muscle strength evaluated using manual and computerized testing methods. This study will be conducted at several CINRG Centers throughout the U.S., Belgium, Israel and Puerto Rico. This study is supported by the Muscular Dystrophy Association. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00016653

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·

KUL0401: An open-label pilot study of Oxatomide in steroid-naive Duchenne muscular dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the safety and efficacy of the mast cell stabilizer Oxatomide as a treatment for Duchenne muscular dystrophy (DMD). Boys with DMD who are enrolled in this study will should not have taken steroids to treat DMD for at least twelve months, and should not have taken any nutritional supplements for at least three months. Subjects will complete a two screening visits within a one-week period, and if enrolled will then have their strength tested monthly for three months before beginning therapy with Oxatomide. Once Oxatomide therapy is started, participants will have their strength tested monthly for six months. Following the six month treatment period, participants will be given the option to remain on Oxatomide until the study is completed. Phase(s): Phase II Study Type: Interventional Contact(s): Erik K Henricson, MPH 202-884-3813 EHenricson@ cnmcresearch.org Diana M Escolar, MD 202-884-6080 DEscolar@ cnmcresearch.org; District of Columbia; Children's National Medical Center, Washington, District of Columbia, 20010, United States; Recruiting; Erik K Henricson, MPH 202-884-3813 EHenricson@ cnmcresearch.org; Diana M Escolar, MD, Principal Investigator Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00033813

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Study of Inherited Neurological Disorders Condition(s): Ataxia; Motor Neuron Disease; Muscular Disease; Muscular Dystrophy; Peripheral Nervous System Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study is designed to learn more about the natural history of inherited neurological disorders and the role of heredity in their development. It will examine the genetics, symptoms, disease progression, treatment, and psychological and behavioral impact of diseases in the following categories: hereditary peripheral neuropathies; hereditary myopathies; muscular dystrophies; hereditary motor neuron


disorders; mitochondrial myopathies; ataxias; hereditary neurocognitive disorders; inherited neurological disorders without known diagnosis; and others. Many of these diseases, which affect the brain, spinal cord, muscles, and nerves, are rare and poorly understood. Children and adults of all ages with various inherited neurological disorders may be eligible for this study. Participants will undergo a detailed medical and family history, and a family tree will be drawn. They will also have a physical and neurological examination that may include blood test and urine tests, an EEG (brain wave recordings), psychological tests, and speech and language and rehabilitation evaluations. A blood sample or skin biopsy may be taken for genetic testing. Depending on the individual patient's symptoms, imaging tests such as X-rays, CT or MRI scans and muscle and nerve testing may also be done. Information from this study may provide a better understanding of the genetic underpinnings of these disorders, contributing to improved diagnosis, treatment, and genetic counseling, and perhaps leading to additional studies in these areas. Study Type: Observational Contact(s): Maryland; National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800411-1222 [email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004568 ·

Randomized Study of Albuterol in Patients with Facioscapulohumeral Muscular Dystrophy Condition(s): Muscular Dystrophy, Facioscapulohumeral Study Status: This study is no longer recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; Ohio State University Purpose - Excerpt: Objectives: I. Determine whether albuterol increases strength in patients with facioscapulohumeral dystrophy as measured by quantitative voluntary isometric contraction testing. II. Determine whether albuterol increases muscle mass in this patient population as determined by 24 hour urinary creatinine excretion and dual energy xray absorptiometry (DEXA). III. Examine the long term safety of albuterol in this patient population. Study Type: Interventional Contact(s): John T. Kissel 614-293-8000. Study chairs or principal investigators: John T. Kissel, Study Chair; Ohio State University

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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004685 ·

Phase III Randomized, Double-Blind Study of Prednisone for Duchenne Muscular Dystrophy Condition(s): Duchenne Muscular Dystrophy Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); National Institute of Neurological Disorders and Stroke (NINDS); University of Rochester Purpose - Excerpt: Objectives: I. Characterize the effect of prednisone on muscle protein metabolism in patients with Duchenne muscular dystrophy. II. Determine whether prednisone changes levels of insulinlike growth factor 1, growth hormone, and insulin. III. Characterize the effect of prednisone on muscle morphometry and muscle localization of utrophin. IV. Compare the prednisone response in patients with Duchenne muscular dystrophy to that seen in normal individuals and in patients with facioscapulohumeral dystrophy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004646

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Study of Muscle Wasting and Altered Metabolism in Patients with Myotonic Dystrophy Condition(s): Muscular Dystrophy Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of Rochester Purpose - Excerpt: Objectives: I. Examine the interrelationships between muscle wasting (phenotype), the degree of myotonic dystrophy (DM) gene expression (genotype) in patients with DM. II. Characterize the insulin resistance in these patients. III. Assess the glucose uptake in the leg and forearm tissues of these patients. IV. Determine the stability of the DM gene lesion in muscles over a 5-10 year period. Study Type: Observational Contact(s):. Study chairs or principal investigators: Richard T. Moxley, III, Study Chair; University of Rochester Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004769


Benefits and Risks

18

What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·

A new treatment could be more effective than the current treatment for muscular dystrophy. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.

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If the treatment is effective, then it may improve health or prevent diseases or disorders.

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Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.

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People who take part in trials contribute to scientific discoveries that may help other people with muscular dystrophy. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent

Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial's risks and benefits, the researcher’s expectations of you, and your rights as a patient.

What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you

This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f2 91. 18

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receive may cause side effects that are serious enough to require medical attention.

How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital's Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent. What Are a Patient's Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·

Information on all known risks and benefits of the treatments in the study.

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Know how the researchers plan to carry out the study, for how long, and where.

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Know what is expected of you.

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Know any costs involved for you or your insurance provider.

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Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.

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Talk openly with doctors and ask any questions.

After you join a clinical trial, you have the right to: ·

Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.

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Receive any new information about the new treatment.

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Continue to ask questions and get answers.


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Maintain your privacy. Your name will not appear in any reports based on the study.

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Know whether you participated in the treatment group or the control group (once the study has been completed).

What about Costs? In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don't have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care. What Should You Ask before Deciding to Join a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·

What is the purpose of the clinical trial?

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What are the standard treatments for muscular dystrophy? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?

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What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?

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How long will the treatment last? How often will I have to come back for follow-up exams?

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What are the treatment's possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?

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Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?

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How will my health be monitored?

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Where will I need to go for the clinical trial? How will I get there?

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How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?

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Will I be able to see my own doctor? Who will be in charge of my care?

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Will taking part in the study affect my daily life? Do I have time to participate?

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How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?

Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to their Web site (www.clinicaltrials.gov) and search by “muscular dystrophy” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm


General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·

A Guide to Patient Recruitment : Today's Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna

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A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna

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The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna

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The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna

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Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna

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Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna

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Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna

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Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta2-adrenergic agonist with its main clinical use in asthma. [NIH] Ataxia: Failure of muscular coordination; irregularity of muscular action. [EU]

Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Gait: Manner or style of walking. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Glucose: D-glucose, a monosaccharide (hexose), C6H12O6, also known as dextrose (q.v.), found in certain foodstuffs, especially fruits, and in the normal blood of all animals. It is the end product of carbohydrate metabolism and is the chief source of energy for living organisms, its utilization being controlled by insulin. Excess glucose is converted to glycogen and stored in the liver and muscles for use as needed and, beyond that, is converted to fat and stored as adipose tissue. Glucose appears in the urine in diabetes mellitus. [EU] Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Heredity: 1. the genetic transmission of a particular quality or trait from parent to offspring. 2. the genetic constitution of an individual. [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator


of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Localization: 1. the determination of the site or place of any process or lesion. 2. restriction to a circumscribed or limited area. 3. prelocalization. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH]

Sclerosis: A induration, or hardening; especially hardening of a part from inflammation and in diseases of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the connective tissue or to designate hardening of the blood vessels. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Urinary: Pertaining to the urine; containing or secreting urine. [EU]

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PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL

ABOUT PART II In Part II, we introduce you to additional resources and advanced research on muscular dystrophy. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on muscular dystrophy. In Part II, as in Part I, our objective is not to interpret the latest advances on muscular dystrophy or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with muscular dystrophy is suggested.

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CHAPTER 4. STUDIES ON MUSCULAR DYSTROPHY Overview Every year, academic studies are published on muscular dystrophy or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on muscular dystrophy. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on muscular dystrophy and teach you how to keep current on new studies as they are published or undertaken by the scientific community.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and muscular dystrophy, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the


format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type in “muscular dystrophy” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search: ·

Inflammatory Myopathies (Polymyositis, Dermatomyositis, Inclusion Body Myositis) Source: Comprehensive Therapy. 24(10): 494-502. October 1998. Summary: This journal article provides health professionals with information on the symptoms, clinical features, laboratory findings, pathology, pathogenesis, differential diagnosis, and treatment of inflammatory myopathies, which are acquired diseases of muscle with various origins. The major inflammatory autoimmune myopathies are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). Patients with inflammatory myopathies characteristically have progressive proximal weakness and wasting. Some patients may also have pain. Patients with DM may also have the classical heliotrope skin rash. Patients with IBM have weakness with early involvement of hand muscles, and they frequently have elevated muscle enzymes in their serum. Although the exact etiology of the inflammatory myopathies is unclear, it has been hypothesized that viral infection triggers the autoimmune process. Laboratory findings include elevated creatine kinase and other muscle enzymes, as well as an elevated erythrocyte sedimentation rate. Some patients have pulmonary fibrosis and an associated neoplasm. Findings on electromyography studies include normal nerve conduction velocities, increased insertional activity, and the presence of denervation potentials at rest on needle examination. The muscle pathology of PM and DM includes necrosis with regeneration and invasion of inflammatory cells into the interstitial and perivascular areas. Muscle biopsy in patients who have IBM shows rimmed vacuoles and necrosis. The differential diagnosis of PM and DM includes other inflammatory myopathies, polymyalgia rheumatica, parasite infection, limb girdle muscular dystrophy, fibromyalgia, chronic fatigue, fasciitis, hypothyroidism, carnitine deficiency, acid maltase deficiency, progressive muscular atrophy, neuropathy, myasthenia gravis, and myopathies from steroids and other drugs. Treatment options include corticosteroids and immunosuppressive agents. 14 figures, 5 tables, and 35 references.

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·

Coenzyme Q10 (Monograph) Source: Alternative Medicine Review. 3(1): 58-61. February 1998. Summary: This monograph on Coenzyme Q10, also known as ubiquinone or CoQ10, contains a review of the biochemistry, pharmacokinetics, and mechanisms of action. It discusses the clinical indication for use of Coenzyme Q10 for several conditions, including cancer, immune system dysfunction, periodontal disease, gastric ulcers, muscular dystrophy, allergies, cardiovascular disease, and diabetes mellitus. Dosage, deficiency of Coenzyme Q10 in the body, toxicity, and drug/nutrient interactions are all described. This monograph contains 1 illustration and 42 references.

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Evaluating the Infant Swallow Source: Advance for Speech-Language Pathologists [and] Audiologists. 7(28): 5, 13. July 14, 1997. Contact: Available from Merion Publications, Inc. 650 Park Avenue, Box 61556, King of Prussia, PA 19406-0956. (800) 355-1088 or (610) 265-7812. Summary: This article describes the steps involved in evaluating the infant swallow. Questions concerning anatomy, maturation, physiology, and neurophysiology remain for researchers and clinicians engaged in studying and diagnosing the infant swallow. Topics include the swallowing risk factors in babies with neurological problems, structural problems that can lead to dysphagia (including laryngeal cleft, congenital achalasia, myotonic dystrophy, cerebral palsy, cranial facial nerve abnormalities, and muscular dystrophy), indications for a videofluorscopy study, calibrating digital fluoroscopy instruments for use on infants and children (in order to reduce the radiation exposure), noninvasive modalities used to study parts of the infant swallow, refusal to eat, psychological components of feeding, and needing to have more speech language pathologists active in the neonatal intensive care unit. The article concludes with the address of the clinician interviewed.

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Effects of Myotonic Dystrophy and Duchenne Muscular Dystrophy on the Orofacial Muscles and Dentofacial Morphology Source: Acta Odontologica Scandanavica. 56(6): 369-374. December 1998. Summary: This article reviews two of the less rare myopathies: myotonic dystrophy (MyD) and Duchenne muscular dystrophy (DMD), and their effect on the orofacial muscles and dentofacial morphology. A high prevalence of malocclusions was found among the patients affected by these diseases. The development of the malocclusions in MyD patients


seems to be strongly related to the vertical aberration of their craniofacial growth due to the involvement of the masticatory muscles in association with the possibly less affected suprahyoid musculature. Thus, a new situation is established around the teeth transversely. The lowered tongue is not in a position to counterbalance the forces developed during the lowering of the mandible by the stretched facial musculature. This may affect the teeth transversely, decreasing the width of the palate and causing posterior crossbite. The lowered position of the mandible, in combination with the decreased biting forces, may permit an overeruption of the posterior teeth, with increased palatal vault height and development of anterior open bite. The development of the malocclusions in DMD patients also seems to be strongly related to the involvement of the orofacial muscles by the disease. However, the posterior crossbite is not developed owing to the narrow maxillary (upper jaw) arch, as is the case in MyD patients. On the contrary, the posterior crossbite in DMD is due to the transversal expansion of the mandibular arch, possibly because of the decreased tonus of the masseter muscle near the molars, in combination with the enlarged hypotonic tongue and the predominance of the less affected orbicularis oris muscle. 2 figures. 33 references. ·

Preliminary Study Into the Dental Health Status of Multiple Sclerosis Patients Source: Special Care in Dentistry. 13(3): 96-101. 1993. Contact: Available from Academy of Dentistry for People with Disabilities. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2661. Summary: This article reports on a preliminary study that examined the dental health status of 22 volunteer patients with Muscular Dystrophy (MS). A questionnaire collected data regarding medical and dental histories and socio-demographic information. Extra-oral and intra-oral examinations were carried out on all subjects to determine the particular dental treatment needs of this group. Instruments used included the Decayed, Missing, or Filled Teeth Index (DMFT) and the Community Periodontal Index of Treatment Needs (CPITN). The DMFT and CPITN scores for this group did not indicate that MS patients were more susceptible to dental caries or periodontal disease. However, the prevalence of trigeminal neuralgia and symptoms of Temporomandibular Joint (TMJ) dysfunction in the group studied indicated that these conditions may be manifest in persons with MS and warrant further investigations. 8 tables 25 references. (AA-M).

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Federally-Funded Research on Muscular Dystrophy The U.S. Government supports a variety of research studies relating to muscular dystrophy and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.19 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally-funded biomedical research projects conducted at universities, hospitals, and other institutions. Visit the CRISP Web site at http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to muscular dystrophy and related conditions. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally-funded studies use animals or simulated models to explore muscular dystrophy and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for muscular dystrophy: ·

Project Title: Dystrophy

Bioengineering

Research

Partnership--Muscular

Principal Investigator & Institution: Sweeney, H L.; Professor and Chairman; Physiology; University of Pennsylvania 1 College Hall Philadelphia, Pa 19104 Timing: Fiscal Year 2000; Project Start 0-SEP-2000; Project End 1-AUG2005 Summary: (Applicant's abstract verbatim) The goal of this BRP is to utilize a number of aspects of bioengineering in order to develop tools and therapeutics for the treatment and monitoring of muscular dystrophies. The project is collaboration between three investigators and includes the following areas of bioengineering relevant to the PA: 1) cell and tissue engineering, 2) imaging and 3) therapeutics. Collectively we will delineate factors that when expressed in muscle may slow that rate of degeneration that is concomitant with either the complete (Duchenne muscular dystrophy) or partial (Becker muscular dystrophy) loss of 19 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).


dystrophin. These studies will utilize the mdx mouse as the animal model for dystrophin deficiency. The long-term goal is to gain the understanding and tools necessary to develop adeno-associated (AAV)based gene therapy for Duchenne and Becker muscular dystrophies. Three parallel lines of investigation (each directed by one of the three investigators) are proposed: Section 1: a dissection the mechanical role of dystrophin and muscle adhesion proteins (directed by Dennis Discher); Section 2: an assessment of the functional benefits of restoring adhesion molecules to dystrophic muscle using recombinant adeno-associated virus gene delivery (directed by H. Lee Sweeney, Ph.D.); and Section 3: development of non-invasive methods for monitoring therapeutic benefits of dystrophin gene transfer (directed by Glenn Walter, Ph.D.). Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Caveolin-3 and Muscular Dystrophy Principal Investigator & Institution: Lisanti, Michael P.; Molecular Pharmacology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2000; Project Start 1-APR-2000; Project End 1-MAR2005 Summary: The long-term objective of this proposal is to understand the role of muscle caveolae and caveolin-3 i) in normal muscle development; and ii) in the pathogenesis of muscle dystrophy. Caveolae are "little caves" at the surface of cells. It has been proposed that caveolae function as message centers" for regulating signal transduction. Caveolin-3, a muscle-specific caveolin-related protein, is the principal structural protein of caveolae membrane domains in striated muscle cell types (cardiac and skeletal). Recently, we identified a novel autosomal dominant form of limb girdle muscular dystrophy (LGMD-1C) in humans that is due to mutations within the coding sequence of the human caveolin-3 gene (3p25). The aim of this proposal is to test the hypothesis that caveolin-3 expression is important for normal muscle development and that changes in caveolin-3 expression (either upregulation or down-regulation) can result in muscular dystrophy phenotype. In order to test this hypothesis,, we will use a variety of complementary in vivo approaches, such as the use of caveolin-3 antisenses in cultured cells and the development of mouse animal models. The specific aims of the project are: 1) To determine the role of caveolin-3 mutations in the pathogenesis of LGMD- 1C. We will examine the phenotypic behavior of LGMD-1C mutations of caveolin-3 after heterologous expression in NIH 3T3 cells, as compared with wild-type caveolin-3; 2) To develop transgenic mouse models that over wild-type caveolin-3 and LGMD-1C mutant forms of caveolin-3. We will over-

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express wild type and LGMD-1C mutant forms of caveolin- 3 as transgenes in mice and assess their effects on skeletal muscle. As caveolin-3 levels are up-regulated in Duchenne's muscular dystrophy, these experiments will help us evaluate if caveolin-3 up-regulation contributes to the pathogenesis of this diseases; and 3) To examine if caveolin-3 expression is required for normal muscle development. Using an anti-sense approach, we will abrogate caveolin-3 expression in C2C12 cells, a skeletal myoblast cell line that differentiates in culture. We will then assess the effects of caveolin-3 down-regulation on C2C12 myoblast fusion and myotube formation. In addition, through a targeted gene disruption approach, we will create and characterize "knock-out" mice that lack caveolin-3 gene expression. It is expected that these studies will contribute fundamen6tal knowledge toward understanding the role of muscle cell caveolae in normal muscle development and muscular dystrophy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Gene Therapy for Duchenne Muscular Dystrophy Principal Investigator & Institution: Wolff, Jon A.; Professor; Pediatrics; University of Wisconsin Madison 500 Lincoln Dr Madison, Wi 53706 Timing: Fiscal Year 2000; Project Start 0-SEP-2000; Project End 1-AUG2005 Summary: (Copied from Applicant Abstract): Gene therapy promises to be a cure for the muscular dystrophies, such as Duchenne muscular dystrophy. Studies by my laboratory and others indicate that the transfer of the normal human dystrophin gene into dystrophic muscle (in the mouse model) prevents the death of the myofiber. The critical problem now is how to deliver the normal dystrophin gene to enough of the muscle cells and have it stably expressed in order to effect a cure. We have spectacular preliminary results that show that plasmid DNA can be delivered via a blood vessel into more than 10 percent of the muscle cells throughout the leg of a rat. This percentage of transfected muscle cells approaches the critical minimum percentage necessary to be curative in children with Duchenne muscular dystrophy. With this approach, multiple administrations should be possible, ensuring that a sufficient number of cells would be converted to dystrophin-positivity. Our studies also indicate that this approach should lead to stable expression of the gene. We have shown that the intravascular injection of naked plasmid DNA (pDNA) into the femoral artery of rats leads to very high foreign gene expression in skeletal muscle throughout the leg and without damaging the muscle. Previous experience with naked DNA and adenoviral vectors showed that the gene transfer efficiency decreased


substantially when going from the young mouse, to adult mouse and then adult rat. The fact that we can achieve very efficient expression in an adult rat is quite encouraging. The objective of this proposal is to extend this approach to larger animals, non-human primates and the dog and its associated Duchenne model. If successful in primates and dogs, a human clinical trial in patients with Duchenne muscular dystrophy could begin in the near future. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Limb Girdle Muscular Dystrophy Gene Therapy Principal Investigator & Institution: Campbell, Kevin P.; ; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2000 Summary: Autosomal recessive limb-girdle muscular dystrophy (ARLGMD) refers to a number of genetically and clinically heterogenous neuromuscular disorders that affect mainly skeletal muscle. Over the last few years, it has become clear that a number of genes encoding protein components of the sarcoglycan complex are responsible for several forms of AR-LGMDs. The sarcoglycans are expressed at the sarcolemma of muscle fibers and, along with other proteins, constitute the dystrophinglycoprotein complex (DGC). These proteins are believed to play a role in maintaining the normal architecture of the muscle cell membrane by constituting a link between the subsarcolemmal cytoskeleton and the extracellular matrix. In particular, we have shown that alpha-sarcoglycan, a 50 kDa component of the DGC, is a deficient in skeletal muscle from patients having limb- girdle muscular dystrophy type 2D, and that the expression of all the other sarcoglycan proteins is also strongly reduced in muscle from these patients. Although these findings constitute great progress in our understanding of the genetic basis for AR-LGMDs, there have been no improvements in the treatment of these invalidating diseases. The long-term goal of this research proposal is the development of a gene transfer strategy for AR-LGMDs. We recently generated an animal model for LGMD2D by disrupting the alpha-sarcoglycan gene in mice and preliminary analyses of homozygous mutant mice indicate that their skeletal muscle displays a dystrophic phenotype, as expected, thus providing a valuable animal mode for LGMD2D. The overall objective of this pilot project is to develop a virally-mediated gene transfer of alphasarcoglycan and to investigate its therapeutic potential in alphasarcoglycan deficient mice. Our first aim will be the construction of recombinant adenovirus and adeno-associated virus vectors containing the human alpha-sarcoglycan deficient mice. Our first aim will be the construction of recombinant adenovirus and adeno-associated virus

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vectors containing the human alpha- sarcoglycan cDNA. These vectors will first be tested for their ability to induce expression of alphasarcoglycan, both in cultured myoblasts and myotubes. We will then proceed to in vivo experiments designed to test the following hypotheses: i) direct intra-muscular injections of adenoviral- based vectors containing the alpha-sarcoglycan cDNA will efficiently allow expression of the protein and restoration of the DGC in of skeletal muscle of mutant mice (Aim 2) and ii) gene transfer of alpha-sarcoglycan will support functional restoration of muscle fibers in these mice (Aim 3). Overall, the experiments outlined in our proposal will yield new information about alpha-sarcoglycan and the potential for virally-mediated alphasarcoglycan gene transfer in mutant mice. In addition, our findings should constitute a foundation for future investigations directed towards developing gene therapy for LGMD2D patients. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Muscle Response to Stress in Canine Muscular Dystrophy Principal Investigator & Institution: Childers, Martin K.; Phys Med and Rehabilitation; University of Missouri Columbia 105 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2000; Project Start 1-MAR-1999; Project End 8-FEB2003 Summary: This project will provide the applicant with the research skills required to develop and assess rehabilitation treatments that enhance function for patients with muscular dystrophy. Throughout a doctoral program in physiology, a major portion of effort will be devoted to a mentored research project which will examine the relationship between mechanical stress and muscle fiber injury in a canine homolog of Duchenne muscular dystrophy. The central hypothesis of this research is that fiber damage in dystrophin-deficient muscle results, in part, from an exaggerated response to mechanical stress incurred during contraction. Furthermore, muscles involved in lengthening contractions are subject to greater stress than other muscles, and are preferentially injured. The central hypothesis will be tested in selected hindlimb muscles of dystrophic dogs by evaluating cellular and physiological features of muscle fiber response to varying levels of imposed stress. Although the mdx mouse is more readily available and a more commonly used experimental model, the dystrophic dog expresses clinical features analogous to humans with Duchenne muscular dystrophy. Aim 1 will correlate muscle membrane damage with myofiber necrosis: Aim 2 will compare regenerative features in muscles involved in lengthening contractions with muscles involved in shortening contractions: Aim 3 will


determine if a lower threshold to stress-induced injury exists in dystrophic fibers compared to controls: and Aim 4 will determine if reducing mechanical stress during growth will eliminate or decrease the exaggerated fiber necrosis and remodeling seen in the adult gastrocnemius muscle. It is anticipated that findings will improve the understanding of how dystrophic muscle responds to physical stress resulting in improved treatment for patients with Duchenne muscular dystrophy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Myeloid Cell Function in Muscular Dystrophy Principal Investigator & Institution: Tidball, James G.; Professor; Physiological Sciences; University of California Los Angeles 405 Hilgard Ave Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 4-SEP-2001; Project End 1-AUG2006 Summary: (provided by applicant): Duchenne muscular dystrophy (DMD) is the most common, inherited, lethal disease of childhood. Although mutations in the dystrophin gene are primarily responsible for DMD and animal models of DMD, many features of dystrophinopathies indicate that secondary processes can contribute substantially to pathology. Recent findings have indicated that the immune system can contribute significantly to the pathological progression of dystrophindeficiency in the mdx mouse model of the disease. The long-term goal of our studies of the pathology of dystrophin-deficiency is to identify the specific immune cells and mechanisms that promote the pathology of dystrophin-deficiencies, after which we will use that information for the development of immune-based therapeutics. Although our preliminary data implicate both myeloid and lymphoid cells in promoting the dystrophic pathology, the studies proposed here will focus on cytotoxic mechanisms that are mediated by macrophages and eosinophils in dystrophic muscle. Our rationale for focusing on these specific myeloid cells is that our preliminary findings strongly implicate these cells in promoting the pathology of dystrophin-deficiency through both innate and acquired immune responses. Our general strategy will be to assess the effect on muscle pathology of depletion of specific myeloid cell populations from the dystrophic mdx mouse. In addition, the effect of those depletions on the lifespan of the dystrophic mdx/utrophindeficient mice will be assessed because these mice die from muscular dystrophy at an early age. We will also test whether introducing null mutations of the inducible nitric oxide synthase gene or major basic protein gene into mdx mice will reduce muscle pathology, because our

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findings implicate cytotoxic pathways in the mdx pathology that involve the products of these genes. Results of the study proposed here will permit us to determine whether therapeutic approaches that are based on reducing myeloid cell mediated pathology can be productive approaches to the treatment of these forms of muscular dystrophy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Calpain Regulation of Muscle Necrosis and Regeneration Principal Investigator & Institution: Spencer, Melissa J.; Assistant Professor; Physiological Sciences; University of California Los Angeles 405 Hilgard Ave Los Angeles, Ca 90024 Timing: Fiscal Year 2000; Project Start 0-SEP-1998; Project End 1-AUG2001 Summary: Many previous investigations have provided correlative data suggesting that calpains play key roles in muscle cell necrosis and regeneration in muscular dystrophy and in muscle cell fusion. However, little experimental data exist to substantiate calpains' hypothetical roles in these processes. In this investigation, transgenic models will be employed to examine the individual roles that the three calpain isoforms play in normal growth and development of muscle, and in the pathological process of mdx dystrophy. This will involve the creation of transgenic mice that overexpress isoforms of calpain in a muscle-specific manner. The investigation proposed here is significant both in the new knowledge that it will contribute to our understanding of the functions of the calpain family of proteases in muscle, but also in providing information that is essential to understanding the pathophysiology of LGMD 2A (Limb Girdle Muscular Dystrophy 2A), which results from a calpain 3 mutation, and DMD (Duchenne Muscular Dystrophy), which involves increased expression and activation of calpains. The following specific aims are to be accomplished in this investigation: Specific Aim 1. Transgenic C57 mice, that overexpress the large subunit of calpains 1, 2 or 3, will be generated to investigate the roles of calpains in normal growth and development of muscle. Specific Aim 2. Transgenic mdx mice, that overexpress the large subunit of calpains 1, 2 or 3, will be generated to investigate the roles of calpains in muscle necrosis, regeneration and repair in muscular dystrophy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Dystrophin Replacement in MDX Mice Principal Investigator & Institution: Chamberlain, Jeffrey S.; Professor; Human Genetics; University of Michigan at Ann Arbor Ann Arbor, Mi 48109


Timing: Fiscal Year 2000; Project Start 1-APR-1991; Project End 1-DEC2000 Summary: (Adapted from applicant's abstract): Duchenne muscular dystrophy (DMD) is an X-linked recessive, lethal disorder caused by mutations in the dystrophin gene. Considerable progress has been made both in understanding the function of dystrophin, and in demonstrating the feasibility of gene therapy for DMD. Nonetheless, numerous obstacles remain before gene therapy can be effectively applied to this common genetic disease. These obstacles include a lack of data on the reversibility of the dystrophic pathology, limited ability of viral vectors to carry the enormous dystrophin gene or cDNA, and questions about the effectiveness of inefficient delivery methods of dystrophin vectors. This application proposes to address these concerns by generating several novel strains of transgenic mice. The ability to modulate the dystrophic phenotype will also be explored using viral delivery of dystrophin and several death protectors to mdx mice, a model for DMD. Transgenic mice that express moderate levels of dystrophin are able to prevent the development of dystrophy in the mdx mouse, a model for DMD. Delivery of adenoviral vectors expressing truncated dystrophins to neonatal, immune tolerant mice can also prevent muscular dystrophy near the site of injection. However, it has not been possible to demonstrate that the pathology can be halted or reversed in adult, dystrophic animals. Aim1 will address the feasibility of reversing muscular dystrophy at different stages of the disease by studying a transgenic mouse line that displays tetracycline-inducible dystrophin expression. Aim 2 will continue previous work aimed at understanding the structural basis of dystrophin functional domains, with the goal of developing severely truncated cDNAs that can be carried by a variety of promising viral vectors, such as adenoassociated viruses (AAV). Currently, the only vectors capable of carrying the full-length dystropin cDNA have problems with cytotoxicity, immune rejection or low titers. AAV efficiently infect muscle with no immune response, but have a limited cloning capacity. Aim 3 explores the ability to modulate dysrtophy by delivery of dystrophin with proteins that repress apoptosis and/or enhance muscle regeneration. Achieving uniform and efficient gene delivery to muscles using viral vectors is a daunting goal. The ability to modulate dystrophy and prolong muscle fiber longevity could greatly facilitate the effectiveness of dystrophin gene replacement strategies. These studies will provide new insights into both the structure of dystrophin and the mechanisms of dystrophic cell death and will help advance the development of gene therapy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Improved Diagnosis of the Muscular Dystrophies Principal Investigator & Institution: Hoffman, Eric P.; James Clark Professor of Pediatrics,; Children's Research Institute 111 Michigan Ave Nw Washington, Dc 20010 Timing: Fiscal Year 2000; Project Start 1-JAN-1991; Project End 0-NOV2003 Summary: This application is the second competitive renewal of this "Improved Diagnostics of the Muscular Dystrophies" grant. During the first award, we showed that primary dystrophinopathies caused the majority of cases of muscular dystrophy, specifically about 80% of male dystrophy patients, and 10% of female dystrophy patients. During the tenure of the second award period (Dec 95-present), we begin dissecting the cause of muscular dystrophy in patients with normal dystrophin. During the last two years, we have investigated muscular dystrophies caused by alpha- sarcoglycan, beta-sarcoglycan, gamma-sarcoglycan, delta-sarcoglycan, merosin, integrin-alpha7, and calpain III. Despite the advances in our understanding of the molecular basis of muscular dystrophy made by our laboratory and others, we can identify the underlying molecular basis for only about 30% of autosomal recessive cases; 70% of patients with normal dystrophin can not be assigned a specific molecular diagnosis. Thus, considerable work remains to identify the many genes causing muscular dystrophy, and this is the focus of this competitive renewal. Our laboratory serves as the major referral site for molecular diagnostics of the muscular dystrophies. Through our for gratis analysis of muscle biopsies for primary dystrophinopathies, and more recently sarcoglycanopathies and merosin disorders, we have assembled what is likely the most extensive tissue-bank of frozen muscle tissue and clinical records of muscular dystrophy patients in the world. 3,049 flash-frozen muscle biopsies from muscular dystrophy patients have been received by the laboratory and fully characterized by the laboratory for dystrophin expression, histopathology, and, in hundreds of cases, gene mutations. It is these well-characterized muscle biopsy specimens which form the starting material for the molecular studies proposed in this renewal application. The goals of this current application are: 1. To continue our successful candidate gene analyses in our large cohort of muscular dystrophy patients; 2. To use the newly emerging GeneChip system (Affymetrix) to determine the changes in gene expression resulting from mutations in specific muscular dystrophy genes as a means to understanding disease progression and pathophysiology; and 3. To use the Gene Chips to identify novel muscular dystrophy genes through specific changes in gene expression. The proposed research will lead to improved understand the etiology of


muscular dystrophies and improved diagnosis of these disorders. The results will enable genetic counseling of patients and their families, and should facilitate efforts directed towards rational therapies. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Laminin Alpha 2 in Tissue Regeneration Principal Investigator & Institution: Engvall, Eva S.; Professor; Burnham Institute 10901 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2000; Project Start 1-MAR-1996; Project End 8-FEB2005 Summary: (Adapted from applicant's abstract) Tissue regeneration and repair are critical to longevity. Insufficient regeneration of muscle and nerve is a significant cause of morbidity in patients with muscular dystrophy and other muscle and nerve diseases and in the aging individual. The laminin subunit a2 is prominently expressed in striated muscle and peripheral nerve, and mutations in the lama2 gene cause a severe form of muscular dystrophy in humans (merosin-deficient congenital muscular dystrophy, MCMD) and mice. A mouse model for human MCMD was generated by disrupting the lama2 gene with the lacZ reporter gene. Homozygous mutant mice develop muscular dystrophy and peripheral neuropathy after birth. Absence of laminin a2 does not significantly affect myogenesis, but the differentiated laminin a2-deficient muscle are highly susceptible to injury upon contraction. Most important, in contrast to the apparent normal development, regeneration is severely compromised in the absence of laminin a2. It is proposed to use in vivo and in vitro models to analyze development and regeneration of skeletal muscle and peripheral nerve to determine which steps in the regeneration process are dependent on laminin a2. The regeneration-promoting effects of laminin a2 will be analyzed in transgenic mice with tissue-specific overexpression of a human LAMA2 transgene. To analyze the molecular pathways responsible for maturation and survival of skeletal muscle and Schwann cells, integrin and dystroglycan signaling pathways will be characterized by using the yeast 2-hybrid screening and affinity chromatography in combination with peptide mass mapping. The proposed research will result in new knowledge regarding important molecular mechanisms of muscle and nerve function and may help in devising new strategies for treatment of degenerative diseases of muscle and nerve based on promoting regeneration. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Molecular Pathophysiology of Facioscapulohumeral Muscul Principal Investigator & Institution: Chen, Yi-Wen; Children's Research Institute 111 Michigan Ave Nw Washington, Dc 20010 Timing: Fiscal Year 2001; Project Start 8-SEP-2001; Project End 1-MAY2004 Summary: (provided by applicant): Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited muscle diseases following Duchenne muscular dystrophy and myotonic dystrophy. The disorder is autosomal dominant with nearly complete penetrance (95%) by age 20. Severity of muscle involvement in FSHD is extremely variable, ranging from elderly individuals with mild facial weakness to wheelchair bound children. Besides variability between individual patients, FSHD patients often show enigmatic asymmetry of muscle involvement. This disease feature permits a novel experimental design, where progression of the disease can be studied within a single patient at a single time point. Previous studies showed a statistically significant correlation between severity of clinical presentation and the deletion of D4Z4 repeats on chromosome 4q35 in patients with FSHD. Current hypotheses center on a position effect of telomeric sequences on genes in or near the deletion site, however the molecular mechanisms underlying this disease are far from clear. In our study, we hypothesize that FSHD patient muscle shows a disease-specific expression profile, relative to other muscle disease (Duchenne muscular dystrophy, alpha-sarcoglycan deficiency, juvenile dermatomyositis, and dysferlin deficiency). In addition, we hypothesize that one can identify a subset of the FSHD-specific genes will be shown to correlate with progression of-muscle involvement in FSHD muscle by comparing expression changes correlated with clinicallyaffected vs. unaffected muscles within single dystrophy patients. In our preliminary data, we have defined an FSHD-specific set of 29 genes that are candidates for primary involvement of disease pathogenesis by using the HuGeneFL array (-6,000 full length genes). In this proposal, we plan to broaden the number of genes studied, so that a genome-wide set of genes implicated in the primary etiology can be defined. Specifically, we will extend our truly promising preliminary data to over 60,000 genes and EST sequences included on the Human genome U95A, B, C, D, E stock chips, as well as the > 2,000 human muscle ESTs on our customproduced MuscleChip. In addition, a custom glass slide array consisting of - 200 genes and ESTs from 4q35 and lOq26 will be used to identify FSHD region specific alterations in gene expression. All FHSD-specific ESTs identified will be characterized in detail. Further studies will likely include the delineation of a complete picture of the pathophysiology of


FSHD, as well as identification of functional SNPs in the refined gene list that correlate with disease severity. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Phase I Clinical Trial Utilizing Gene Therapy for LGMD Principal Investigator & Institution: Kissel, John; Ohio State University Columbus, Oh 43210 Timing: Fiscal Year 2000; Project Start 1-DEC-1976; Project End 0-NOV2001 Summary: We propose to evaluate the safety of the gene therapy in Limb girdle muscular dystrophy, specifically alpha-sarcoglycan deficiency, using a recombinant, replication-deficient, adeno-associated viral delivery system. The primary objective of this study is to determine the safety of adeno-associated virus (AAV) delivered via needle injection into the extensor digitorum (EDB) muscle. The EDB is a small foot muscle without important function. Muscles on both feet will be injected. One foot will receive the alpha-sarcoglycan gene and the other an injection of sterile saline. This will be done in a double-blind manner without the investigators or the patient's knowledge of which side is receiving the gene vs placebo. Six weeks after injection both EDB muscles will biopsied to determine if the gene has been effective in replacing the missing protein. This will be the first human trial of gene therapy for any type of muscular dystrophy. Currently there is no medication that is known to be effective for the treatment of any of the forms of LGMD. If this study is successful, it will represent the first step in a series of studies directed more toward efficacy of gene therapy in this disease. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

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Project Title: Role of the Alpha 7 Beta 1 Integrin in Muscle Integrity Principal Investigator & Institution: Kaufman, Stephen J.; Professor; Cell and Structural Biology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 4-JAN-1997; Project End 1-AUG2006 Summary: (provided by applicant): The proper association of muscle fibers with laminin in the extracellular matrix is essential for normal muscle function. The alpha7Beta1 integrin and the dystrophinglycoprotein complex both bind laminin and appear to be complementary linkage systems between fibers and the extracellular matrix. Congenital and acquired defects in the dystrophin-glycoprotein complex underlie the pathology associated with Duchenne and other

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muscular dystrophies, as well as cardiomyopathies. Mutations in the human alpha7 gene cause an additional myopathy. We recently discovered that enhanced expression of the alpha7 integrin mediated linkage system can compensate for the absence of the dystrophinglycoprotein complex. Dystrophin/utrophin null mice develop an acute muscular dystrophy and die prematurely. Enhanced expression of the alpha7 integrin inhibits the development of muscular dystrophy and restores longevity to these animals. We propose to expand on this result and determine the level of alpha7Beta1 integrin that best prevents development of skeletal muscle pathology in these animals and whether transgene expression in the heart and smooth muscle can prevent cardiovascular disease. We will also analyze whether enhanced expression of the alpha7 integrin in the heart reduces development of cardiomyopathy associated with enterovirus-induced cleavage of dystrophin. Additional skeletal muscle and cardiomyopathies result from other defects in the dystrophin-glycoprotein linkage system. We will use transgenic animals that over-express the alpha7Beta1 integrin in different genetic backgrounds to determine whether the integrin can prevent these myopathies. Whereas mutations in the sarcoglycan genes perturb the dystrophin-glycoprotein transmembrane linkage system and cause cardiomyopathy and muscular dystrophy, we will determine whether over-expression of the alpha7 integrin can inhibit the development of muscle disease in sarcoglycan deficient mice. Likewise, we will assess whether enhanced integrin expression will ameliorate alpha2-laminin congenital muscular dystrophy. Lastly, experiments are proposed that aim at understanding the mechanism by which enhanced integrin expression inhibits development of muscle pathology. This research will reveal whether increasing alpha7 integrin levels in humans may be worth pursuing in the future as treatments for Duchenne and other muscular dystrophies and cardiomyopathies. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·

Project Title: Structure-Function Analysis of Sarcospan Principal Investigator & Institution: Crosbie, Rachelle H.; Duchenne Musc Dyst Res Ctr; University of California Los Angeles 405 Hilgard Ave Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 4-SEP-2001; Project End 1-AUG2006 Summary: (provided by applicant): The broad, long-term objectives of this proposal are to understand the structure and function of a novel tetraspanin called SARCOSPAN. Sarcospan is an integral component of the dystrophin-glycoprotein complex and is highly expressed in skeletal


and cardiac muscles, as well as many non-muscle tissues (Crosbie et al., 1997; Crosbie et al., 1998; Crosbie et al., 1999). The dystrophinglycoprotein complex (DGC) is a structural complex that spans the muscle plasma membrane and links the extracellular matrix with the intracellular cytoskeleton. This structural linkage is critical for normal muscle function as clearly demonstrated by the many forms of muscular dystrophy that result from mutations in the dystrophin-glycoprotein complex. Association of several signaling molecules with the DGC also suggests that this complex may play a role in mediating extracellularintracellular communications. Furthermore, lateral associations amongst membrane components of the DGC are critical for function of this complex. It is hypothesized that sarcospan facilitates protein-protein interactions within the dystrophin-glycoprotein complex. These protein interactions are clearly important for the physical linkage between the extracellular matrix and the intracellular actin network and for the prevention of muscular dystrophy. Human mutations within the sarcospan gene have not been identified in known cases of autosomal recessive muscular dystrophy (Crosbie et al., 2000). However, these mutation searches have only examined the ubiquitous form of SSPN, which has a broad expression pattern. Preliminary data demonstrates that a novel, muscle-specific form of SSPN is expressed in skeletal and cardiac muscles. We hypothesize that mutations within muscle-SSPN may cause novel forms of muscular dystrophy. Identification and characterization of this muscle-sarcospan will advance our understanding of the role of the dystrophin-glycoprotein complex in normal muscle and in the pathogenesis of muscular dystrophy. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket

E-Journals: PubMed Central20 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).21 Access to this growing archive of e-journals is free and unrestricted.22 To search, go

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html. 21 With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 22 The value of PubMed Central, in addition to its role as an archive, lies the availability of data from diverse sources stored in a common format in a single repository. Many journals 20

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to http://www.pubmedcentral.nih.gov/index.html#search, and type “muscular dystrophy” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for muscular dystrophy in the PubMed Central database: ·

A 71-Kilodalton Protein is a Major Product of the Duchenne Muscular Dystrophy Gene in Brain and Other Nonmuscle Tissues by D Lederfein, Z Levy, N Augier, D Mornet, G Morris, O Fuchs, D Yaffe, and U Nudel; 1992 June 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49288

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A second promoter provides an alternative target for therapeutic upregulation of utrophin in Duchenne muscular dystrophy by Edward A. Burton, Jonathon M. Tinsley, Paul J. Holzfeind, Nanda R. Rodrigues, and Kay E. Davies; 1999 November 23 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=24184

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Brain dystrophin-glycoprotein complex: Persistent expression of betadystroglycan, impaired oligomerization of Dp71 and up-regulation of utrophins in animal models of muscular dystrophy by Kevin Culligan, Louise Glover, Paul Dowling, and Kay Ohlendieck; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=29067

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Commentary:NO skeletal muscle derived relaxing factor in Duchenne muscular dystrophy by David S. Bredt; 1998 December 8 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=33925

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Detection of Dystrophin in the Postsynaptic Density of Rat Brain and Deficiency in a Mouse Model of Duchenne Muscular Dystrophy by T Kim, K Wu, J Xu, and IB Black; 1992 December 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=50609

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From the Cover:Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model by Bing Wang, Juan Li, and Xiao Xiao; 2000 December 5 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17641

already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.


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Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy by Mikael Sander, Bahman Chavoshan, Shannon A. Harris, Susan T. Iannaccone, James T. Stull, Gail D. Thomas, and Ronald G. Victor; 2000 December 5 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17659

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Neuronal Nitric Oxide Synthase and Dystrophin-Deficient Muscular Dystrophy by W Chang, ST Iannaccone, KS Lau, BSS Masters, TJ McCabe, K McMillan, RC Padre, MJ Spencer, JG Tidball, and JT Stull; 1996 August 20 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=38609

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Possible Influences on the Expression of X Chromosome-Linked Dystrophin Abnormalities by Heterozogosity of Autosomal Recessive Fukuyama Congenital Muscular Dystrophy by AH Beggs, PE Neumann, K Arahata, E Arikawa, I Nonaka, MS Anderson, and LM Kunkel; 1992 January 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48291

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Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy by Rossella Tupler, Giovanni Perini, Maria Antonietta Pellegrino, and Michael R. Green; 1999 October 26 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23032

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Social deprivation in Duchenne muscular dystrophy: population based study by Kate Bushby, Simon Raybould, Sara O'Donnell, and James G Steele; 2001 November 3 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=59456

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The role of basal and myogenic factors in the transcriptional activation of utrophin promoter A: implications for therapeutic up-regulation in Duchenne muscular dystrophy by Kelly J. Perkins, Edward A. Burton, and Kay E. Davies; 2001 December 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=96689&ren dertype=external

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Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype by Ferruccio Galbiati, Daniela Volonte, Jeffrey B. Chu, Maomi Li, Samson W. Fine, Maofu Fu, Jorge Bermudez, Marina Pedemonte, Karen M. Weidenheim, Richard G. Pestell, Carlo Minetti, and Michael P. Lisanti; 2000 August 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=16926

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Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI by Olga Camacho Vanegas, Enrico Bertini, Rui-Zhu Zhang, Stefania Petrini, Claudia Minosse, Patrizia Sabatelli, Betti Giusti, Mon-Li Chu, and Guglielmina Pepe; 2001 June 19 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=34700

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine. The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to the public.23 If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with muscular dystrophy, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “muscular dystrophy” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “muscular dystrophy” (hyperlinks lead to article summaries): ·

Breathing exercises for children with pseudohypertrophic muscular dystrophy. Author(s): Houser CR, Johnson DM. Source: Physical Therapy. 1971 July; 51(7): 751-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=4933570&dopt=Abstract

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Cell transplantation as an experimental treatment for Duchenne muscular dystrophy. Author(s): Law PK, Goodwin TG, Fang Q, Deering MB, Duggirala V, Larkin C, Florendo JA, Kirby DS, Li HJ, Chen M, et al.

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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Source: Cell Transplantation. 1993 November-December; 2(6): 485-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8167934&dopt=Abstract

Vocabulary Builder Acuity: Clarity or clearness, especially of the vision. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Pertaining to the heart and blood vessels. [EU] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Collagen: The protein substance of the white fibres (collagenous fibres) of skin, tendon, bone, cartilage, and all other connective tissue; composed of molecules of tropocollagen (q.v.), it is converted into gelatin by boiling. collagenous pertaining to collagen; forming or producing collagen. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior

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(in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alphaactinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes. [NIH] Enterovirus: A genus of the family picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated "human enterovirus". [NIH] Enzyme: A protein molecule that catalyses chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions. Enzymes are classified according to the recommendations of the Nomenclature Committee of the International Union of Biochemistry. Each enzyme is assigned a recommended name and an Enzyme Commission (EC) number. They are divided into six main groups; oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [EU] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU]


Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrosis: The formation of fibrous tissue; fibroid or fibrous degeneration [EU] Fluoroscopy: screen. [NIH]

Production of an image when x-rays strike a fluorescent

Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Masticatory: 1. subserving or pertaining to mastication; affecting the muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Membrane: A thin layer of tissue which covers a surface, lines a cavity or divides a space or organ. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes; it may affect groups of cells or part of a structure or an organ. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH]

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Neuralgia: Paroxysmal pain which extends along the course of one or more nerves. Many varieties of neuralgia are distinguished according to the part affected or to the cause, as brachial, facial, occipital, supraorbital, etc., or anaemic, diabetic, gouty, malarial, syphilitic, etc. [EU] Neuropathy: A general term denoting functional disturbances and/or pathological changes in the peripheral nervous system. The etiology may be known e.g. arsenical n., diabetic n., ischemic n., traumatic n.) or unknown. Encephalopathy and myelopathy are corresponding terms relating to involvement of the brain and spinal cord, respectively. The term is also used to designate noninflammatory lesions in the peripheral nervous system, in contrast to inflammatory lesions (neuritis). [EU] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Perivascular: Situated around a vessel. [EU] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Pharmacokinetics: The action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of YEASTS. [NIH] Prophylaxis: The prevention of disease; preventive treatment. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]

Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pulmonary: Pertaining to the lungs. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU]

Sedimentation: The act of causing the deposit of sediment, especially by the


use of a centrifugal machine. [EU] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]

Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals. [NIH]

Ulcer: A local defect, or excavation, of the surface of an organ or tissue; which is produced by the sloughing of inflammatory necrotic tissue. [EU] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viruses: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. [NIH]

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CHAPTER 5. PATENTS ON MUSCULAR DYSTROPHY Overview You can learn about innovations relating to muscular dystrophy by reading recent patents and patent applications. Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.24 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available to patients with muscular dystrophy within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available to patients with muscular dystrophy. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information.

24Adapted

from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.


Patents on Muscular Dystrophy By performing a patent search focusing on muscular dystrophy, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on muscular dystrophy: ·

Gene replacement therapy for muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Holt; Kathleen H. (Corlville, IA), Duclos; Franck (Iowa City, IA), Lim; Leland E. (Iowa City, IA), Straub; Volker (Essen, IA), Davidson; Beverly (Iowa City, IA), Williamson; Roger (Iowa City, IA) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 6,262,035 Date filed: October 1, 1998 Abstract: Disclosed is a method for treating a patient suffering from the disease sarcoglycan-deficient limb-girdle muscular dystrophy by gene replacement therapy. Sarcoglycan gene replacement therapy produces extensive long-term expression of the sarcoglycan species which restores the entire sarcoglycan complex, results in the stable association of alph.alpha.-dystroglycan with the sarcolemma, and eliminates the morphological markers of limb-girdle muscular dystrophy. In another aspect, the invention relates to a method for determining a specific defective sarcoglycan species in the tissue of a patient. The method involves culture of muscle cells obtained from the patient, and the independent introduction of expression vectors encoding each of the sarcoglycan species, .alpha., .beta., .gamma., and .delta., into the cultured cells with subsequent assaying for restoration of the dystrophinglycoprotein complex. In another aspect, the invention relates to a mouse, and cells derived therefrom, homozygous for a disrupted .alpha.sarcoglycan gene. The disruption prevents the synthesis of functional .alpha.-sarcoglycan in cells of the mouse and results in the mutant mouse having no detectable sarcospan, .beta.-, .gamma.-, .delta.-sarcoglycan, and reduced .alpha.-dystroglycan in the sarcolemma of skeletal and

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cardiac muscles, and a reduction of dystrophin in skeletal muscle, when compared to tissue of a mouse lacking a disrupted .alpha.-sarcoglycan gene. In another aspect, the invention relates to methods for screening for therapeutic agents useful in the treatment of sarcoglycan-deficient limbgirdle muscular dystrophy. The methods involve administering a candidate therapeutic agent to a mouse, or cells derived therefrom, and assaying for therapeutic effects on the mouse or cells, with the determination of therapeutic effects being a reduction or reversal in disease progression, or a restoration of the dystroglycan complex. Excerpt(s): The term muscular dystrophy describes a group of diseases characterized by hereditary progressive muscle weakness and degeneration. Several muscular dystrophies are caused by mutations in genes that encode sarcolemmal proteins, including certain types of limbgirdle muscular dystrophy (LGMD). LGMD is genetically and clinically heterogeneous; it may be inherited in an autosomal dominant or recessive manner, and may have different rates of progression and severity. A unifying theme among the LGMDs is the initial involvement of the shoulder and pelvic girdle muscles, with relative sparing of most other muscle groups (Jackson et al., Pediatrics 41, 495-501 (1968); Bushby, K. M., Neuromusc Disord 5, 71-74 (1995)). ... The pace of discovery in the field of muscular dystrophy research has been rapid since the discovery of the Duchenne and Becker muscular dystrophy (DMD) gene in 1986 (Monaco et al., Nature 323, 646-650 (1986)). The DMD gene encodes dystrophin, a large cytoskeletal protein that together with other molecular components makes up the dystrophin-glycoprotein complex (DGC). The dystrophin-glycoprotein complex (DGC) is a large oligomeric complex of sarcolemmal proteins and glycoproteins in skeletal and cardiac muscle (Campbell, K. P. Cell 80, 675-679 (1995); Ozawa et al., Hum. Mol. Genet. 4, 1711-1716 (1995)). This complex consists of dystrophin, a large cytoskeletal protein which binds F-actin; .alpha.- and .beta.-dystroglycan, which bind laminin and the cysteine-rich region of dystrophin, respectively; .alpha.-, .beta.-, .gamma.-, and .delta.sarcoglycan (.delta.-SG), which form a distinct subcomplex; and sarcospan, a 25 kDa protein predicted to span the membrane four times (Crosbie et al., J. Biol. Chem. 272, 31221-31224 (1997). The DGC spans the sarcolemma and is believed to play an essential role in maintaining the normal architecture of the muscle sarcolemma by constituting a link between the subsarcolemmal cytoskeleton and the extracellular matrix. This structural linkage is thought to protect muscle fibers from the mechanical stress of contraction. ... Mutations in different components of the DGC lead to similar dystrophic features, suggesting that the function of the DGC as a whole is dependent on intact molecular interactions between its individual subunits. The loss of one component destroys the


link, and leads to muscle fiber degeneration. Several components of the DGC have been implicated in several human muscular dystrophies (Straub et al., Curr. Opin. Neurol. 10, 168-175 (1997)). Mutations in dystrophin cause Duchenne and Becker muscular dystrophy (DMD) (Hoffman et al., Cell 51, 919-928 (1987)). Two forms of congenital muscular dystrophy are caused by mutations in the extracellular matrix protein laminin 2 (Helbling-Leclerc et al., Nature Genet. 11, 216-218 (1995); Allamand et al., Hum. Mol. Genet. 6, 747-752 (1997)). Mutations in each of .alpha.-, .beta.-, .gamma.-, and .delta.-SG cause autosomal recessive LGMD types 2D, 2E, 2C, and 2F, respectively (Roberds et al., Cell 78, 625-633 (1994); Piccolo et al., Nature Genet. 10, 243-245 (1995); Lim et al., Nature Genet. 11, 257-265 (1995); Bonneman et al., Nature Genet. 11, 266-273 (1995); Noguchi et al., Science 270, 819-822 (1995); Passos-Bueno et al., Hum. Mol. Genet. 5, 815-820 (1996); Nigro et al., Hum. Mol. Genet. 5, 1179-1186 (1996); Nigro et al., Nature Genet. 14, 195198 (1996)). Web site: http://www.delphion.com/details?pn=US06262035__ ·

Method for aiding in the diagnosis of in-frame deletion type congenital muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Allamand; Valerie (Iowa City, IA), Sunada; Yoshihide (Kawaguchi, JP), Straub; Volker (Iowa City, IA), Salih; Mustafa (Riyadh, SA) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 6,136,546 Date filed: April 9, 1998 Abstract: Disclosed are compositions and methods for aiding in the diagnosis of congenital muscular dystrophy associated with in-frame deletion in the laminin-2 .alpha.2 polypeptide chain in an individual. In a preferred diagnostic method embodiment, an experimental muscle tissue sample is provided from the individual and treated if necessary to render components available for antibody binding. The components of the sample are then separated on the basis of molecular weight. The separated protein components are then transferred to a solid support while maintaining the relative positions established in separation step. The transferred components are then stained with an affinity reagent which is known to bind to a C-terminal domain of the laminin-2 .alpha.2 polypeptide chain. Individual afflicted with congenital muscular dystrophy associated with in-frame deletion in the laminin-2 .alpha.2 polypeptide chain on the basis of positive staining in combination with

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reduced molecular weight of the laminin-2 .alpha.2 polypeptide chain relative to the wild-type laminin-2 .alpha.2 polypeptide chain. A preferred composition is a nucleic acid probe for the detection of merosin deletion-type congenital muscular dystrophy. The preferred nucleic acid probe is characterized by the ability to bind specifically to a mutant merosin nucleic acid sequence, the mutant merosin nucleic acid sequence comprising a T to C substitution at position 3973 +2 of the consensus donor splice site of exon 25. Excerpt(s): Laminins are a family of large extracellular glycoproteins which display a complex and still unclear repertoire of biological functions. Laminin-2, the isoform involved in congenital muscular dystrophy (CMD), is specifically expressed in the basal lamina of striated muscle and peripheral nerve. As are all members of the laminin family, it is composed of three chains: one heavy (.alpha.2) and two light chains (.beta.1 and .gamma.1) that assemble in a cross-shaped molecule with three short arms and one long arm. The C-terminal ends of each chain interact to form the triple stranded long arm of the molecule, stabilized by disulfide bonds, with a large globular (G) domain contributed to by the .alpha.2-chain. The .alpha.2-chain of laminin consists of 6 domains: I and II are part of the long arm; IIIa, IIIb and V contain cystein-rich EGFlike repeats and are predicted to have rigid rod-like structures; and IVa, IVb and VI are predicted to form globular structures. Laminin .alpha.2chain has been shown to be a native ligand for .alpha.-dystroglycan, an extracellular component of the dystrophin-associated glycoprotein complex (DGC). This complex constitutes a link between the subsarcolemmal skeleton and the extracellular matrix. A number of components of the DGC have now been shown to be involved in muscular dystrophies suggesting a crucial role of laminin-2 and the components of the DGC in maintaining the integrity of muscle cell function. ... Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of autosomal recessive neuromuscular disorders of early onset. In the classic form of CMD, clinical manifestations are limited to skeletal muscle with no clinical involvement of the central nervous system (CNS) although changes in the white matter have been detected by MRI. The histological changes in muscle biopsies consist of connective tissue proliferation, large variation in the size of the muscle fibers as well as some necrotic and regenerating fibers. ... The present invention relates to compositions and methods for aiding in the diagnosis of congenital muscular dystrophy associated with inframe deletion in the laminin-2 .alpha.2 polypeptide chain in an individual. In a preferred diagnostic method embodiment, an experimental muscle tissue sample is provided from the individual and treated if necessary to render components available for antibody binding.


The components of the sample are then separated on the basis of molecular weight. The separated protein components are then transferred to a solid support while maintaining the relative positions established in separation step. The transferred components are then stained with an affinity reagent which is known to bind to a C-terminal domain of the laminin-2 .alpha.2 polypeptide chain. Individual afflicted with congenital muscular dystrophy associated with in-frame deletion in the laminin-2 .alpha.2 polypeptide chain on the basis of positive staining in combination with reduced molecular weight of the laminin-2 .alpha.2 polypeptide chain relative to the wild-type laminin-2 .alpha.2 polypeptide chain. Web site: http://www.delphion.com/details?pn=US06136546__ ·

Merosin deficiency-type congenital muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Sunada; Yoshihide (Iowa City, IA), Tome; Fernando M. S. (Paris, FR), Fardeau; Michel (Sceaux, FR) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 5,863,743 Date filed: August 12, 1994 Abstract: Disclosed is a method for aiding in the diagnosis of merosin deficiency-type congenital muscular dystrophy (CMD). The method is based on the discovery of a previously unidentified form of CMD which is characterized by a substantial reduction in the levels of merosin in skeletal muscle tissue containing normal levels of dystrophin and dystrophin-associated proteins. Excerpt(s): Congenital muscular dystrophy (CMD), a very disabling muscle disease of early clinical onset, is the most frequent cause of severe neonatal hypotonia. Its manifestations are noticed at birth or in the first months of life and consist of muscle hypotonia, often associated with delayed motor milestones, severe and early contractures and joint deformities. Serum creatine kinase is raised, up to 30 times the normal values, in the early stage of the disease, and then rapidly decreases. The histological changes in the muscle biopsies consist of large variation in the size of muscle fibers, a few necrotic and regenerating fibers, marked increase in endomysial collagen tissue, and no specific ultrastructural features. The diagnosis of CMD has been based on the clinical picture and the morphological changes in the muscle biopsy, but it cannot be made with certainty, as other muscle disorders may present with similar clinico-pathological features. ... Within the group of diseases classified as CMD, various forms have been individualized. The two more common

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forms are the occidental and the Japanese, the latter being associated with severe mental disturbances, and usually referred to as Fukuyama congenital muscular dystrophy (FCMD). The genetic lesion responsible for FCMD has recently been mapped to chromosome 9. It is unknown whether or not the rare cases of CMD associated with mental retardation or central nervous system abnormalities observed in occidental countries belong to the same disease entity. The determination of the gene (or genes) responsible for the various forms of CMD is required in order to clearly delineate specific members of the currently ill-defined genus. ... The present invention is based on the identification of a novel disease etiology which is responsible for a previously undefined member of the congenital muscular dystrophy family. The novel etiology, referred to herein as merosin deficiency-type congenital muscular dystrophy, was identified through the study of levels of specific proteins in mammalian muscle tissue. Web site: http://www.delphion.com/details?pn=US05863743__ ·

Method of in vitro preconditioning healthy donor's myoblasts before transplantation thereof in compatible patients suffering of recessive myopathies like muscular dystrophy, for improving transplantation success Inventor(s): Tremblay; Jacques P. (Bernieres, CA) Assignee(s): Universite Laval (Quebec, CA) Patent Number: 5,833,978 Date filed: March 16, 1995 Abstract: A method of pretreating healthy donor's myoblast cultures with growth or trophic factors like basic fibroblast growth factor (bFGF) on transplantation to subjects suffering of recessive myopathy like muscular dystrophy is disclosed and claimed. Recipient muscles show a higher percentage of functional cells, demonstrated by the higher incidence of dystrophin-positive fibers, and does not require previous preconditioning of recipient muscles by irradiation or toxin administration. Donor mouse myoblasts expressing the reporter gene .beta.- galactosidase were grown with 100 ng/ml bFGF during the last two days before injecting them in the left tibialis anterior (TA) muscles of recipient MHC-compatible mdx mice, an experimental animal model of muscular dystrophy. Myoblasts from the same primary cultures were also grown without bFGF and injected in the right TA muscles as control. The recipient mice were immunosuppressed with FK 506. Twenty-eight days after myoblast transplantation, the percentage of .beta.-


galactosidase-positive fibers was significantly higher (more than a 4 fold increase) following culture with bFGF than without bFGF. Almost all .beta.-galactosidase-positive-fibers were also dystrophin positive. Excerpt(s): The present invention is a method for preconditioning healthy donor's myoblasts in vitro before transplantation thereof in compatible patients suffering of recessive myopathies, particularly of muscular dystrophy. This in vitro preconditioning improves the success of the transplantation while not requiring an in vivo preconditioning of the patient's muscle by irradiation or by administering muscular toxin. ... Duchenne muscular dystrophy (DMD) is a progressive disease characterized by the lack of dystrophin under the sarcolemmal membrane.sup.6,19,28,37. One possible way to introduce dystrophin in the muscle fibers of the patients to limit the degeneration is to transplant myoblasts obtained from normal subjects.sup.30,34,35. Several groups have tried myoblast transplantations to DMD patients but poor graft success was observed.sup.17,22,24,38. Even in experimental myoblast transplantation using mdx mice, an animal model of DMD.sup.10,25,29, large amount of dystrophin-positive fibers were observed only when nude mdx mice were previously irradiated to prevent regeneration of the muscle fibers by host myoblasts.sup.32,43. High percentage of dystrophin-positive fibers was also observed in mdx mice immunosuppressed with FK 506 and in SCID mice, in both cases muscles were previously damaged by notexin injection and irradiated.sup.23,27. These results indicate that to obtain successful myoblast transplantation, it is necessary to have not only an immunodeficient mouse or a mouse adequately immunosuppressed but also a host muscle which has been adequately preconditioned. It is, however, impossible in clinical studies to use damaging treatments such as marcaine, notexin and irradiation. If good myoblast transplantation results can be obtained without using such techniques, this would be very helpful for myoblast transplantation in humans. ... The present invention relates to a method of in vitro preconditioning of myoblasts harvested from healthy donor's biopsy prior to their transplantation in patients affected by recessive myopathies, particularly by Duchenne muscular dystrophy (DMD). In a DMD animal model (mdx), compatible donor mouse myoblasts were grown in culture with muscular growth or trophic factors, particularly, basic Fibroblast Growth Factor (bFGF), before transplanting them in muscles of mdx mice without any previous damaging treatment. A four fold increase in the percentage of muscle fibers expressing dystrophin, which is indicative of functional muscle cells, was obtained with pretreatment with bFGF. These experimental results are expected to verify in naturally occurring dystrophy or other types of recessive myopathies in animal and human

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subjects, since the mdx mouse is an animal model wherein muscular dystrophy is naturally occurring. Web site: http://www.delphion.com/details?pn=US05833978__ ·

Changes in laminin subunit composition are diagnostic of Fukuyama congenital muscular dystrophy Inventor(s): Engvall; Eva (Rancho Santa Fe, CA), Arahata; Kiichi (Tokyo, JP) Assignee(s): La Jolla Cancer Research Foundation (La Jolla, CA) Patent Number: 5,780,244 Date filed: February 14, 1994 Abstract: The present invention relates to a method for detecting altered expression or localization of a cytoskeleton/basal lamina protein in a tissue sample obtained from an individual, wherein the altered expression or localization are associated with a muscular dystrophy such as Fukuyama congenital muscular dystrophy (FCMD). The invention provides an immunohistochemical method for detecting the expression and localization in a tissue, such as muscle, of laminin M (merosin), which is a protein component of the basal lamina, wherein certain defined changes are diagnostic of individuals predisposed to FCMD. The invention also provides a prenatal diagnostic screening procedure, using a tissue such as placenta, wherein the screening procedure can identify an individual predisposed to FCMD. The invention further provides methods for identifying an individual predisposed to other muscular dystrophies such as Walker-Warburg Syndrome (WWS) and muscle-eyebrain disease of the Finnish type (MEB). Excerpt(s): This invention relates generally to the field of medicine and more specifically to methods for detecting changes in the expression of laminin M protein and of M chain mRNA that are diagnostic of Fukuyama congenital muscular dystrophy (FCMD). The invention further relates to methods of identifying agents that can reduce or prevent the symptoms associated with FCMD and to methods of treating an FCMD patient. ... Primary deficiencies of protein components of the membrane cytoskeleton of muscle fibers include dystrophin and dystrophin-glycoprotein complexes, which are detected in Duchenne and Becker Muscular Dystrophy (Ibraghimov-Beskrovnaya et al. (1992); Ervasti et al., Nature 345:315-319 (1990); Ervasti and Campbell, Cell 66:1121-1131 (1991); Yoshida and Ozawa, J. Biochem. 108:748-752 (1990)). Secondary deficiencies also occur. For example, the laminin-binding 156 kdal DAG is markedly reduced in human Duchenne muscular dystrophy


(DMD) and in muscle obtained from mdx mice, which are the murine equivalent of Duchenne/Becker muscular dystrophy in humans (Ervasti et al. (1990)). The lack of dystrophin protein in mdx mouse is due to a mutation in the dystrophin gene (Bulfield 1984), Hoffman et al., 1987). Although the mdx mouse has a much milder phenotype than human patients with dystrophin defects has provided a useful model system for studying the molecular mechanisms responsible for DMD in humans. ... Other forms of muscular dystrophy in humans are known. For example, a deficiency of a 50 kdal DAG component of the membrane cytoskeleton was observed in an autosomal recessive form of muscular dystrophy that is prevalent in North Africa (Matsumura et al., Nature 359:320-322 (1992)). Fukuyama congenital muscular dystrophy (FCMD) is an autosomal recessive form of congenital muscular dystrophy that is endemic to Japan and has an incidence of 6.9-11.9 per 100,000 births. FCMD is characterized by progressive muscle wasting and dystrophic muscle pathology. In addition, central nervous system involvement results in profound mental retardation associated with abnormal brain pathology such as neuronal and glial heterotopias (Kamoshita et al., Arch. Neurol. 33:513-516 (1976); Stern and Manson, Devel. Med. Child Neurol. 32:808-813 (1988); Fukuyama et al., Brain Devel. 13:1-29 (1981)). Other forms of muscular dystrophy such as muscle-eye-brain disease of the Finnish type (MEB) and Walker-Warburg Syndrome (WWS) also occur as autosomal recessive diseases and may be a result of the same genetic defect as FCMD ((Cook et al., J. Child. Neurol. 7:S51-63 (1992); Osawa et al., Acta Paediatr. (Japan) 33:261-269 (1991); Lenard, H. G., Acta Paediatr. (Japan) 33:256-260 (1991); Miller et al., Acta Neuropathol. (Berlin) 82:234-238 (1991); Yoshioka et al., Brain Devel. 12:423-426 (1990)). Web site: http://www.delphion.com/details?pn=US05780244__ ·

Diagnosis of myotonic muscular dystrophy Inventor(s): Caskey; C. Thomas (West University, TX), Fu; Ying-Hui (Columbus, OH), Friedman; David L. (Houston, TX), Pizzuti; Antonio (Milan, IT), Fenwick; Raymond G. (Sugarland, TX) Assignee(s): Baylor College of Medicine (Houston, TX) Patent Number: 5,552,282 Date filed: June 6, 1993 Abstract: The present invention includes a DNA clone from the myotonic muscular dystrophy gene, a cosmid probe to the myotonic dystrophy site, as well as methods of detecting myotonic muscular dystrophy using RFLP. The method involves the steps of digesting DNA from an

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individual to be tested with a restriction endonuclease and detecting the restriction fragment length polymorphism with hybridization to probes within the myotonic muscular locus and southern blot analysis. Alternatively, the myotonic muscular dystrophy gene can be measured by determining the amount of mRNA or measuring the amount of protein with an antibody. Further, the myotonic muscular dystrophy gene defect can be detected using either fluorescence in situ hybridization or pulsed field gel electrophoresis using the probes described herein. Excerpt(s): This invention relates to the field of molecular diagnosis of myotonic muscular dystrophy. ... The myotonic muscular dystrophy (DM) disease is the most common adult muscular dystrophy in man with a prevalence of 1 in 10,000. The disorder is inherited in an autosomal dominant manner with variable expression of symptoms from individual to individual within a given family. Furthermore, the phenomenon of anticipation (increasing disease severity over generations) is well documented for DM. This is particularly evident when an affected mother transmits the gene for the disease to her offspring. These offspring have a high incidence of mental retardation and profound infantile myotonia. Adult patients with DM manifest a pleiotropic set of symptoms including myotonia, cardiac arrhythmias, cataracts, frontal baldness, hypogonadism, and other endocrine dysfunctions. There is no evidence that myotonic muscular dystrophy may be caused by defects in more than one gene. ... A myotonic muscular dystrophy gene has been mapped to human chromosome position 19q13.3. Both a genetic and physical map of the region was developed by a group of investigators acting as a voluntary consortium under sponsorship of the Muscular Dystrophy Association. The genetic linkage studies identified two RFLP alleles, D10 and X75, which are polymerase chain reaction (PCR)-based dinucleotide polymorphisms and are tightly linked to DM. Web site: http://www.delphion.com/details?pn=US05552282__ ·

Method of treatment for muscular dystrophy Inventor(s): Antoku; Yasunobu (Kurume, JP), Tsukamoto; Kosuke (Kurume, JP), Koike; Fumihiko (Saga, JP), Sakai; Tetsuo (Yame, JP), Tanaka; Kaoru (Fukuoka, JP) Assignee(s): MinoPhagen Pharmaceutical Company (Tokyo, JP) Patent Number: 5,434,142 Date filed: August 24, 1993 Abstract: Administering to a patient of muscular dystrophy a pharmaceutical agent containing glycyrrhizin and/or a pharmaceutically


acceptable salt thereof as effective components is effective against muscular dystrophy, particularly, Duchenne or Becker muscular dystrophy and is highly safe with less side effect. Excerpt(s): This invention relates to a method of treatment for muscular dystrophy and, more particularly, to a method of treatment for muscular dystrophy such as Duchenne muscular dystrophy, Becker muscular dystrophy and the like. ... The Duchenne muscular dystrophy is a sexlinked recessive disease occuring in childhood, in which muscle weakness and muscular wasting in the proximal parts of extremities and trunk are progressed, resulting in a death at about twenty. The Becker muscular dystrophy is also a sex-linked recessive disease showing the same symptoms, although its onset age is older and tile progression is slower, compared with the Duchenne type. ... Other muscular dystrophies include limb-girdle muscular dystrophy, facioscapulohumeral (FSH) muscular dystrophy, congenital muscular dystrophy, and the like. Web site: http://www.delphion.com/details?pn=US05434142__ ·

Measuring dystrophy

non-dystrophin

proteins

and

diagnosing

muscular

Inventor(s): Campbell; Kevin P. (Iowa City, IA), Ervasti; James M. (Iowa City, IA), Ohlendieck; Kay (Iowa City, IA), Gaver; Mitchell G. (Cockeysville, MD), Kahl; Steven D. (Iowa City, IA) Assignee(s): University of Iowa Research Foundation (Iowa City, IA) Patent Number: 5,413,910 Date filed: October 7, 1992 Abstract: The invention pertains to the dystrophin-glycoprotein complex of mammalian skeletal muscle and a method of isolating said complex. The components of the complex and methods of separating and isolating said components also pertain to the invention. In addition, the invention further relates to a method of diagnosing muscular dystrophy by detecting and quantifying the loss of a non-dystrophin component of the dystrophin-glycoprotein complex with said loss being indicative of muscular dystrophy. Excerpt(s): Muscular dystrophy refers to a group of genetically determined myopathies characterized by progressive atrophy or degeneration of increasing numbers of individual muscle cells. The structural changes observed histologically are essentially the same in the various types of muscular dystrophies. This may, perhaps, suggest a

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common etiology. However, the distribution of the affected muscles is quite distinctive. This, along with the mode of inheritance, forms the basis of the classification of these diseases. The muscular dystrophies are traditionally subdivided by the patterns of initial muscle involvement, which in turn correlates fairly well with the type of genetic transmission. The three major forms of muscular dystrophy are as follows: 1) Duchenne's Muscular Dystrophy which affects most skeletal muscle groups and is transmitted by an X-linked recessive gene; 2) Limb Girdle Muscular Dystrophy, affecting principally the pelvic and shoulder girdle muscles and is transmitted by an autosomal recessive gene; and 3) Facioscapulohumeral Muscular Dystrophy, involves the muscles of the face and shoulder girdle and is transmitted by an autosomal dominant gene. ... Recently, the defective gene responsible for Duchenne's Muscular Dystrophy (DMD) has been located on the X-chromosome. The DMD gene encodes for a large molecular weight protein product, called dystrophin. This protein is localized to the sarcolemmal membrane of normal skeletal muscle, but is absent from the skeletal muscle of people with DMD, as well as dogs and mice with dystrophic muscle. A more benign form of this X-linked recessive disease is Becker's Muscular Dystrophy which is caused by an abnormal DMD gene which encodes an abnormal dystrophin protein. The exact function of dystrophin and the reasons why its absence or abnormal structure results in necrosis of dystrophic muscle fibers have not been determined. However, the amino acid sequence of dystrophin suggests that it is a membrane cytoskeletal protein. ... The present technology for initial detection and diagnosis of Duchenne's or Becker's Muscular Dystrophy relies on the use of an immunological probe to identify the presence of dystrophin, the absence of dystrophin, or the abnormal molecular weight or content of dystrophin in human muscle biopsies. It is not uncommon for genetic diseases to involve the loss or abnormal synthesis of more than one component or protein. In the case of muscular dystrophy, proteins other than dystrophin may be involved which are translated from genes located on different chromosomes (X chromosomes and/or autosomal chromosomes), resulting in the different forms of muscular dystrophy. The identification of other potential proteins involved in muscular dystrophy and methods of quantifying these proteins would be immensely useful to clinicians for confirming diagnosis of Duchenne's and Becker's muscular dystrophy, as well as perhaps providing an initial diagnosis of other forms of muscular dystrophy. In addition, knowledge of the function of these proteins may lead to methods of predicting prognosis of disease progression and perhaps therapeutic treatments for patients with muscular dystrophy in all of its various forms. Web site: http://www.delphion.com/details?pn=US05413910__


·

Method for assaying a human muscular dystrophy protein Inventor(s): Ishiguro; Tsuneo (Kawasaki, JP), Eguchi; Chikahiko (Kawasaki, JP) Assignee(s): Ajinomoto Co., Inc. (Tokyo, JP) Patent Number: 5,340,718 Date filed: January 27, 1993 Abstract: Methods and polypeptides for assaying human proteins associated with Duchenne muscular dystrophy, are disclosed. Excerpt(s): The present invention relates to a method for assaying dystrophin which is a protein defective in a human suffering from Duchenne muscular dystrophy (DMD) which is a hereditary disease. ... Duchenne muscular dystrophy is a hereditary disease which is developed almost only in males. A gene which is defective peculiarly to this disease is located on the X chromosome and its sequence has been elucidated [M. Konig, E. P. Hoffman, C. J. Bertelson, A. P. Monaco, C. Feenet and L. M. Kunkel: Cell, 50, 509 (1987), E. P. Hoffman, A. P. Monaco, C. C. Feeher and L. M. Kunkel, Science, 238, 347 (1987)]. If any antibody capable of specifically recognizing dystrophin which is a protein encoded by this gene is produced, a deletion or defect of dystrophin specific to this disease could be detected and such would be useful. A related method was tried by Hoffman et al., using the gene from mice suffering from a disease which is the same type as Duchenne muscular dystrophy [E. P. Hoffman, R. H. Brown, Jr. and L. M. Kunkel, Cell, 51, 919 (1987); E. P. Hoffman, C. M. Knudson, K. P. Campbell and L. M. Kunkel, Nature, 330, 754 (1987)]. However, the method of Hoffman et al. uses a gene from mice, the amino acid sequence of which is different by about 10% from that of humans, to produce the antibody so that it is inappropriate to determine dystrophin possessed by humans. Moreover, according to this method, protein having a high molecular weight such as 208 amino acid residues or 410 amino acid residues is used as an antigen and hence, the method has a shortcoming that an antibody capable of reacting not only with dystrophin but also with many other proteins is formed and that the antibody fails to specifically react with dystrophin alone. In order to compensate for the poor specificity of reaction, Hoffman et al. adopted a method using a specimen obtained by previously homogenizing cells to be tested followed by separating protein from the homogenate by electrophoresis, and then performing an antigen-antibody reaction with respect to the specimen. For this reason, the method encounters a drawback that operations are complicated and is thus unsatisfactory. ... In general, conventional methods for assaying dystrophin have drawbacks in that antibodies capable of specifically

Patents 99

reacting only with dystrophin could not be obtained since a gene from a mouse, which is different from that of a human, has been used for preparation of the antibody. Further, operations are complicated since the method comprises using a specimen obtained by previously homogenizing cells to be tested and separating protein from the homogenate by electrophoresis and performing an antigen-antibody reaction with respect to the specimen. Therefore, the present inventors have made extensive investigations to discover a method for assaying the protein in cells in a simple manner, by preparing an antiserum capable of specifically reacting only with dystrophin or an antibody fraction separated from the antiserum using a part of dystrophin encoded by human Duchenne muscular dystrophy-associated gene and performing an antigen-antibody reaction between a substance to be tested and the antiserum or antibody fraction. Web site: http://www.delphion.com/details?pn=US05340718__ ·

Diagnosis of autosomal muscular dystrophy Inventor(s): Campbell; Kevin P. (Iowa City, IA), Matsumura; Kiichiro (Iowa City, IA) Assignee(s): Univ. of Iowa Research Foundation (Oakdale, IA) Patent Number: 5,308,752 Date filed: September 14, 1992 Abstract: Disclosed are methods for the diagnosis of autosomal muscular dystrophy through the analysis of muscle tissue using antibodies reactive with components of the dystrophin-glycoprotein complex. An experimental muscle tissue sample, treated if necessary to render components of the dystrophin-glycoprotein complex available for antibody binding, is contacted with an antibody which binds to a dystrophin-associated protein. The extent of antibody binding is determined, and compared to the extent of antibody binding to normal control tissue. A substantial reduction in the extent of binding to experimental tissue, as compared with normal control tissue, being diagnostic of autosomal muscular dystrophy. Among the autosomal muscular dystrophies which are detectable by the methods described herein are Fukuyama muscular dystrophy and severe childhood autosomal recessive muscular dystrophy. Excerpt(s): Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a disease which is prevalent in North Africa. This progressive muscular dystrophy shares several clinical features with Duchenne's muscular dystrophy (DMD) including, for example, mode of


onset, rapid progression, hypertrophy of calves and extremely high serum creatine kinase levels during the initial stages of the disease (see, e.g., Ben Hamida et al., J. Neurol Sci. 107: 60-64 (1992)). ... It has been demonstrated that Duchenne's muscular dystrophy is caused by a mutation or deletion which results in the absence of the dystrophin protein (Hoffman et al., Cell 51: 919-928 (1987)). Dystrophin has been shown to be associated with a large oligomeric complex of sarcolemmal glycoproteins (see, e.g., Ervasti and Campbell, Cell 66: 1121-1131 (1991)). The dystrophin-glycoprotein complex has been proposed to span the sarcolemma and provide a linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. In DMD, the absence of dystrophin leads to a great reduction in all of the dystrophin-associated proteins. These observations have enabled, for example, the development of immunologically-based methods for the diagnosis of DMD. ... The subject invention relates to methods for the diagnosis of autosomal muscular dystrophy through the analysis of muscle tissue using antibodies reactive with components of the dystrophin-glycoprotein complex. An experimental muscle tissue sample, treated if necessary to render components of the dystrophin-glycoprotein complex available for antibody binding, is contacted with an antibody which binds to a dystrophin-associated protein. The extent of antibody binding is determined, and compared to the extent of antibody binding to normal control tissue. A substantial reduction in the extent of binding to experimental tissue, as compared with normal control tissue, has been determined to be diagnostic of autosomal muscular dystrophy. Web site: http://www.delphion.com/details?pn=US05308752__ ·

Muscular dystrophy protein, dystrophin Inventor(s): Kunkel; Louis M. (Hyde Park, MA), Monaco; Anthony (Boston, MA), Hoffman; Eric P. (Newton, MA), Koenig; Michel (Boston, MA) Assignee(s): The Children's Medical Center Corporation (Boston, MA) Patent Number: 5,239,060 Date filed: December 22, 1987 Abstract: The invention relates to a muscular dystrophy (MD) probe comprising a substantially purified single-stranded nucleic acid sequence capable of hybridizing to a region of DNA on a human X chromosome between the deletion break point at Xp21.3 and the translocation break point at X;11. The invention also relates to a 14 kb cDNA corresponding to the complete MD gene and probes produced therefrom useful in

Patents 101

genetic methods of diagnosis of MD. Furthermore, the invention relates to the polypeptide, dystrophin, which corresponds to the MD gene product, and antibodies thereto that are useful in a variety of methods for immunodiagnosis of MD. Excerpt(s): Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder which affects about 1 in 3,300 males. Traits associated with DMD (DMD phenotype) are well known and may include elevated creatine phosphokinase levels in serum (at least 10.times. the normal level), delayed development of motor function, and muscle weakness characterized by the replacement of muscle fiber with adipose and fibrose tissue accompanied by a marked variation in muscle size. Until recently, carrier identification in DMD families generally was accomplished by detecting elevated levels of creatine phosphokinase in serum. ... Becker muscular dystrophy (BMD) is also an X-linked recessive genetic disorder, but occurs at only 10% of the frequency of DMD. BMD is a more benign form of muscular dystrophy which follows a less rapid clinical course than DMD. Both DMD and BMD are caused by mutations in the DMD gene located in the Xp21 region of the short arm of the human X chromosome. ... Outlier muscular dystrophy (OMD) is a mild Duchenne/severe Becker disorder. It forms a subgroup that comprises approximately 10 percent of individuals inflicted with DMD. Web site: http://www.delphion.com/details?pn=US05239060__ ·

Use of isopropylaminopyrimidine in the chemotherapy of muscular dystrophy, myopathy and myotonia Inventor(s): Huve; Pierre M. (3, rue Cernushi, 75017 Paris, FR) Assignee(s): none reported Patent Number: 4,416,885 Date filed: March 22, 1982 Abstract: A method for the chemotherapy of muscular dystrophy which includes administrating orally an effective amount of 2 isopropylaminopyrimidine. Excerpt(s): The present invention is directed to a new use of an existing compound. U.S. Pat. No. 4,073,895 relates to the use of a substituted salt of 2-aminopyrimidine. This patent in fact teaches that a particular salt of 2-aminopyrimidine, namely 2-isopropylaminopyrimidine orthophosphate (IAPP), is useful as an active agent for the treatment of neuropathies. Although this use is known, the particular efficacy of the salt against muscular dystrophy has yielded encouraging results. ... The


invention broadly comprises a method for the chemotherapy of muscular dystrophy, which comprises administering either orally or by injection or administering by any method known to those skilled in the art an effective dosage of 2-isopropylaminopyrimidine or therapeutically acceptable salts of the same or the hydroxylated and oxygenated metabolites thereof. ... The dystrophic chicken homozygote was used for monitoring chemotherapy of muscular dystrophy. This particular animal line inherits dystrophy in a form as close as possible in causation and course to human dystrophy and also permits quantitative assessment of progress of the disease by several independent methods. Web site: http://www.delphion.com/details?pn=US04416885__ ·

Use of isopropylaminopyrimidine in the chemotherapy of muscular dystrophy, myopathy and mytonia Inventor(s): Huve; Pierre M. (Paris, FR) Assignee(s): Societe d'Etudes de Produits Chimiques (FR) Patent Number: 4,344,947 Date filed: October 29, 1980 Abstract: A method for the chemotherapy of muscular dystrophy which includes administrating an effective amount of 2 isopropylaminopyrimidine. Excerpt(s): The present invention is directed to a new use of an existing compound. U.S. Pat. No. 4,073,895 relates to the use of a substituted salt of 2 aminopyrimidine. This patent in fact teaches that a particular salt of 2 aminopyrimidine, namely 2 isopropylaminopyrimidine orthophosphate (IAPP), is useful as an active agent for the treatment of neuropathies. Although this use is known, the particular efficacy of the salt against muscular dystrophy has yielded unexpected and superior results. ... The invention broadly comprises a method for the chemotherapy of muscular dystrophy, which comprises administering an effective dosage of 2 isopropylaminopyrimidine or therapeutically acceptable salts of the same or the hydroxylated and oxygenated metabolites thereof. ... The dystrophic chicken homozygote was used for monitoring chemotherapy of muscular dystrophy. This particular animal line inherits dystrophy in a form as close as possible in causation and course to human dystrophy and also permits quantitative assessment of progress of the disease by several independent methods. Web site: http://www.delphion.com/details?pn=US04344947__

Patents 103

Patent Applications on Muscular Dystrophy As of December 2000, U.S. patent applications are open to public viewing.25 Applications are patent requests which have yet to be granted (the process to achieve a patent can take several years). The following patent applications have been filed since December 2000 relating to muscular dystrophy: ·

Pharmaceutical composition for treatment of duchenne muscular dystrophy Inventor(s): Matsuo, Masafumi ; (Kobe-shi, JP) Correspondence: Greenblum & Bernstein, P.L.C.; 1941 Roland Clarke Place; Reston; VA; 20191; US Patent Application Number: 20010056077 Date filed: July 31, 2001 Abstract: A therapeutic pharmaceutical composition for patients of Duchenne muscular dystrophy with entire loss of exon 20 in dystrophin mature mRNA is provided. The composition comprise as an active principle an antisense oligonucleotide consisting of a 20 to 50-nucleotide sequence against exon 19 of the dystrophin pre-mRNA. Excerpt(s): The present invention relates to the use of an antisense oligonucleotide for the manufacture of a therapeutic pharmaceutical composition for a certain hereditary disease, and more specifically to a therapeutic pharmaceutical composition for Duchenne muscular dystrophy intended to induce an exon skipping in the pre-mRNA of a certain abnormal dystrophin gene. ... Today, diagnosis has become available for some hereditary diseases caused by abnormal splicing of the corresponding pre-mRNA, and an intractable disease, muscular dystrophy, has come to draw particular attention. Muscular dystrophy is grossly classified into Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is a hereditary muscular disease of highest incidence, occurring in one out of 3,500 newborn boys. Patients of DMD exhibit lowered muscular power in their infancy at first, and, after suffering from consistent muscular atrophy from then on, eventually die at the age of about 20. At present, no effective therapeutic drug is available for DMD, and therefore development of such a therapeutic has been longed for by patients all over the world. In 1987, dystrophin gene as the causative gene of DMD was found with the aid of retrospective genetics, and BMD also was found to occur from abnormality of the same dystrophin gene [Koenig, M. et al., Cell, 50:509-517(1987)]. As for BMD,

25

This has been a common practice outside the United States prior to December 2000.


its onset is relatively late, which is noted in the adulthood, and, though a mild loss of muscular power is observed after the onset of the disease, nearly normal life is allowed. ... Thus, the present invention provides use of an antisense oligonucleotide for the manufacture of a therapeutic pharmaceutical composition for Duchenne muscular dystrophy with entire loss of exon 20 in the production of dystrophin mature mRNA, wherein said antisense oligonucleotide consists of a 20 to 50-nucleotide sequence against exon 19 of the dystrophin pre-mRNA. Use of such an antisense oligonucleotide as an active principle for a therapeutic pharmaceutical composition makes it possible, for a type of Duchenne muscular dystrophy having an entire loss of exon 20, to shift the amino acids reading frame in its mRNA from abnormal out-of-frame position to in-frame one, and this then enables to convert the disease to a less severe Becker muscular dystrophy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with muscular dystrophy, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “muscular dystrophy” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on muscular dystrophy. You can also use this procedure to view pending patent applications concerning muscular dystrophy. Simply go to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.

Vocabulary Builder Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Antibody: An immunoglobulin molecule that has a specific amino acid

Patents 105

sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it. Antibodies are classified according to their ode of action as agglutinins, bacteriolysins, haemolysins, opsonins, precipitins, etc. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized Tlymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Benign: Not malignant; not recurrent; favourable for recovery. [EU] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Homozygote: identical. [NIH]

An individual in which both alleles at a given locus are

Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hypertrophy: Nutrition) the enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells. [EU] Lesion: Any pathological or traumatic discontinuity of tissue or loss of


function of a part. [EU] Localization: 1. the determination of the site or place of any process or lesion. 2. restriction to a circumscribed or limited area. 3. prelocalization. [EU] Metabolite: process. [EU]

Any substance produced by metabolism or by a metabolic

Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU]

Books 107

CHAPTER 6. BOOKS ON MUSCULAR DYSTROPHY Overview This chapter provides bibliographic book references relating to muscular dystrophy. You have many options to locate books on muscular dystrophy. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some patients, however, feel uncomfortable approaching their local booksellers and prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on muscular dystrophy include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go to http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “muscular dystrophy” (or synonyms) into the “For these words:” box. You will only receive results on books. You should check back periodically with this database which is updated every 3 months. The following is a typical result when searching for books on muscular dystrophy:


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A-Z Reference Book of Syndromes and Inherited Disorders Source: London, England: Chapman and Hall. 1996. 394 p. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 2386777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. PRICE: $42.95 plus shipping and handling. ISBN: 0412641208. Summary: This book provides a practical reference for both caregivers and those with a syndrome or inherited disorder. The author describes the disorders and problems of both children and adults, and considers the day-to-day management of conditions. The book is written in nontechnical language while still providing enough detail for medical, nursing, and midwifery professionals. The syndromes and disorders are listed alphabetically by name. Those specifically related to deafness, communication, and speech and language include achondroplasia, Alport's syndrome, Apert's syndrome, Asperger's syndrome, Batten's disease, Beckwith-Wiedeman syndrome, CHARGE syndrome, Cockayne syndrome, Cornelia de Lange syndrome, Crouzon's syndrome, Down's syndrome, Duchenne muscular dystrophy, Edward's syndrome, EhlersDanlos syndrome, Fabry disease, fetal alcohol syndrome, Fragile X syndrome, Gilles de la Tourette syndrome, Goldenhar syndrome, Hunter's syndrome, Hurler's syndrome, Klinefelter's syndrome, LEOPARD syndrome, Moebius syndrome, Morquio's syndrome, neurofibromatosis, Niemann-Pick disease, Noonan's syndrome, osteogenesis imperfecta, Pierre-Robin syndrome, Prader-Willi syndrome, Rett's syndrome, Reye's syndrome, San Filippo syndrome, SmithMagenis syndrome, Stickler syndrome, Tay-Sachs disease, Treacher Collins syndrome, Turner's syndrome, Usher's syndrome, Waardenburg's syndrome, and William's syndrome. For each syndrome, the author lists alternative names, incidence, causation (etiology), characteristics or symptoms, management implications (treatment options), prognosis, and self-help groups to contact. Most groups listed are in England. The book concludes with three appendices that provide a discussion of genetics, a listing of regional genetics centers (in England), and a glossary of terms. A subject index is also included. (AA-M).

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes & Noble.com, offer summaries which have been supplied by each title’s

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publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ). The following have been recently listed with online booksellers as relating to muscular dystrophy (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·

Muscular Dystrophy Research: Advances and New Trends (International Congress Vol 527) by Howard Griffin (1980); ISBN: 044490168X; http://www.amazon.com/exec/obidos/ASIN/044490168X/icongroupi nterna

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Muscular Dystrophy : Proceedings of the International Symposium on Muscular Dystrophy, Held November 25-27, 1980 in Tokyo by International Symposium on Muscular Dystrophy (1983); ISBN: 0860083217; http://www.amazon.com/exec/obidos/ASIN/0860083217/icongroupin terna

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Muscular Dystrophy : Biomedical Aspects by S. and Ozawa, E. Ebashi (Editor) (1983); ISBN: 0387123423; http://www.amazon.com/exec/obidos/ASIN/0387123423/icongroupin terna

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Psychosocial Aspects of Muscular Dystrophy and Allied Diseases: Commitment to Life, Health, and Function by Leon I. Charash (1983); ISBN: 0398048118; http://www.amazon.com/exec/obidos/ASIN/0398048118/icongroupin terna

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Muscular Dystrophy and Allied Diseases : Impact on Patients, Family, and Staff (Current Thanatology) by Leon I. Charash (1985); ISBN: 0930194381; http://www.amazon.com/exec/obidos/ASIN/0930194381/icongroupin terna

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Readings in Muscular Dystrophy (1986); ISBN: 0895684020; http://www.amazon.com/exec/obidos/ASIN/0895684020/icongroupin terna

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Readings in Muscular Dystrophy by Douglas H. Ruben, Nancy R. MacCiomei (Editor) (1986); ISBN: 0582286581; http://www.amazon.com/exec/obidos/ASIN/0582286581/icongroupin terna

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Readings Muscular Dystrophy by Douglas Ruben (1986); ISBN: 058228659X;


http://www.amazon.com/exec/obidos/ASIN/058228659X/icongroupi nterna ·

Ventilators and Muscular Dystrophy by Nancy C. Schock (1987); ISBN: 0931301033; http://www.amazon.com/exec/obidos/ASIN/0931301033/icongroupin terna

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Pathogenesis and Therapy of Duchenne and Becker Muscular Dystrophy by Byron A. Kakulas, Frank L. Mastaglia (Editor) (1990); ISBN: 0881675970; http://www.amazon.com/exec/obidos/ASIN/0881675970/icongroupin terna

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Muscular Dystrophy Research : From Molecular Diagnosis Toward Therapy : Proceedings (International Congress Series, No. 934) by A. Angelini, et al (1991); ISBN: 044481406X; http://www.amazon.com/exec/obidos/ASIN/044481406X/icongroupi nterna

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Muscular Dystrophy and Other Neuromuscular Disease : Psycholsocial Issues by Leon I. Charash, et al (1991); ISBN: 1560240776; http://www.amazon.com/exec/obidos/ASIN/1560240776/icongroupin terna

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The Will to Live: The Battle of a Young Boy Against Muscular Dystrophy by A.J. Mills (1992); ISBN: 0963392107; http://www.amazon.com/exec/obidos/ASIN/0963392107/icongroupin terna

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Duchenne Muscular Dystrophy : Animal Models and Genetic Manipulation by Byron Kakulas, et al (1992); ISBN: 0881679380; http://www.amazon.com/exec/obidos/ASIN/0881679380/icongroupin terna

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Molecular and Cell Biology of Muscular Dystrophy (Molecular and Cell Biology of Human Diseases, No 3) by Terence Partridge (Editor) (1993); ISBN: 0412434407; http://www.amazon.com/exec/obidos/ASIN/0412434407/icongroupin terna

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Multiple Sclerosis, Muscular Dystrophy & Als (Dr. Donsbach Tells You What You Need to Know About) by Kurt W. Donsbach, H. Rudolph Alseleben (1993); ISBN: 1569595666; http://www.amazon.com/exec/obidos/ASIN/1569595666/icongroupin terna

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Myoblast Transfer : Gene Therapy for Muscular Dystrophy (Medical Intelligence Unit) by Peter K. Law (1994); ISBN: 1879702762;

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http://www.amazon.com/exec/obidos/ASIN/1879702762/icongroupin terna ·

Duchenne Muscular Dystrophy by Alan E. Emery (1996); ISBN: 0192617982; http://www.amazon.com/exec/obidos/ASIN/0192617982/icongroupin terna

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Living With Muscular Dystrophy: Illness Experience, Activities of Daily Living, Coping, Quality of Life & Rehabilitation (Comprehensive Summaries Of) by Birgitta Natterlund (2001); ISBN: 9155449972; http://www.amazon.com/exec/obidos/ASIN/9155449972/icongroupin terna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “muscular dystrophy” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:26 ·

Abstracts of communications: Eighth Symposium on Current Research in Muscular Dystrophy and Allied Neuromuscular Diseases, held at the University of Newcastle upon Tyne 3-5 January 1980. Author: Symposium on Current Research in Muscular Dystrophy and Allied Neuromuscular Diseases (8th: 1980: University of Newcastle upon Tyne); Year: 1980; London: Muscular Dystrophy Group of Great Britain, [1980?]

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Amyotrophic lateral sclerosis and other motor neuron diseases. Author: editor, Lewis P. Rowland; Year: 1991; New York: Raven Press, c1991; ISBN: 0881677485

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a “Books” button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Cellular and molecular biology of muscle development: proceedings of a Muscular Dystrophy Association-UCLA Symposium, held at Steamboat Springs, Colorado, April 3-10, 1988. Author: editors, Laurence H. Kedes, Frank E. Stockdale; Year: 1989; New York: Liss, c1989; ISBN: 084512692X http://www.amazon.com/exec/obidos/ASIN/084512692X/icongroupi nterna

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Composition and function of cell membranes: application to the pathophysiology of muscle diseases. Author: edited by Stewart Wolf and Allen K. Murray; Year: 1981; New York: Plenum, c1981; ISBN: 030640883X http://www.amazon.com/exec/obidos/ASIN/030640883X/icongroupi nterna

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Current research in muscular dystrophy, Japan: clinical researches; the proceedings of the Annual Meeting of Muscular Dystrophy Research Group, 1980, Tokyo. Author: Muscular Dystrophy Research Group (Japan). Meeting (1980: Tokyo, Japan); Year: 1981; [Tokyo?: s.n., 1981?]

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Current research in muscular dystrophy, Japan: the proceedings of the Annual Meeting of Muscular Dystrophy Research Group, 1978, 1979, Tokyo. Author: Muscular Dystrophy Research Group (Japan). Meeting (1978-1979: Tokyo, Japan); Year: 1980; [Tokyo?: s.n., 1980?]

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Disorders of the motor unit. Author: edited by Donald L. Schotland; Year: 1982; New York: Wiley, 1982; ISBN: 0471095079 http://www.amazon.com/exec/obidos/ASIN/0471095079/icongroupin terna

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Duchenne muscular dystrophy: animal models and genetic manipulation. Author: editors, Byron A. Kakulas, John McC. Howell, Allen D. Roses; Year: 1992; New York: Raven Press, c1992; ISBN: 0881679380 http://www.amazon.com/exec/obidos/ASIN/0881679380/icongroupin terna

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Duchenne muscular dystrophy. Author: Alan E.H. Emery; Year: 1993; Oxford; New York: Oxford University Press, 1993; ISBN: 0192623702 (hbk) http://www.amazon.com/exec/obidos/ASIN/0192623702/icongroupin terna

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Gene expression in muscle. Author: edited by Richard C. Strohman and Stewart Wolf; Year: 1985; New York: Plenum Press, c1985; ISBN: 0306418940

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Genetic analysis of the X chromosome: studies of Duchenne muscular dystrophy and related disorders. Author: edited by Henry F. Epstein and Stewart Wolf; Year: 1982; New York: Plenum Press, c1982; ISBN: 0306411296 http://www.amazon.com/exec/obidos/ASIN/0306411296/icongroupin terna

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History of a genetic disease: Duchenne muscular dystrophy or Meryon's disease. Author: Alan E.H. Emery & Marcia L.H. Emery; Year: 1995; London; New York: Royal Society of Medicine Press, c1995; ISBN: 1853152493

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Molecular and cell biology of muscular dystrophy. Author: edited by Terence Partridge; Year: 1993; London; New York: Chapman & Hall, 1993; ISBN: 0412434407 (hardback: alk. paper) http://www.amazon.com/exec/obidos/ASIN/0412434407/icongroupin terna

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Multiple sclerosis, muscular dystrophy & ALS. Author: Kurt W. Donsbach, H. Rudolph Alsleben; Year: 1993; [United States]: Rockland Corp., c1993; ISBN: 1569595666 http://www.amazon.com/exec/obidos/ASIN/1569595666/icongroupin terna

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Muscular dystrophy: biomedical aspects. Author: edited by Setsuro Ebashi and Eijiro Ozawa; Year: 1983; Tokyo: Japan Scientific Societies Press; Berlin; New York: Springer-Verlag, 1983; ISBN: 0387122423 (SpringerVerlag: U.S.)

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Muscular dystrophy: methods and protocols. Author: edited by Katherine M.D. Bushby and Louise V.B. Anderson; Year: 2001; Totowa, N.J.: Humana Press, c2001; ISBN: 0896036952 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0896036952/icongroupin terna

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Muscular dystrophy: proceedings of the International Symposium on Muscular Dystrophy, held November 25-27, 1980, in Tokyo. Author: edited by Setsuro Ebashi; Year: 1982; [Tokyo]: University of Tokyo Press, c1982; ISBN: 0860083217 http://www.amazon.com/exec/obidos/ASIN/0860083217/icongroupin terna

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Muscular dystrophy and other inherited diseases of skeletal muscle in animals. Author: edited by John B. Harris; Year: 1979; New York: New York Academy of Sciences, 1979; ISBN: 0897660056



Muscular dystrophy and other neuromuscular diseases: psychosocial issues. Author: Leon I. Charash ... [et al.], editors; Jill C. Crabtree, editor for the Foundation of Thanatology; Year: 1991; New York: Haworth Press, c1991; ISBN: 1560240776 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/1560240776/icongroupin terna

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Muscular dystrophy research: advances and new trends: proceedings ... Author: editors, C. Angelini, G.A. Danieli, D. Fontanari; Year: 1980; Amsterdam; Princeton, N.J.: Excerpta medica, 1980

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Muscular dystrophy research: from molecular diagnosis toward therapy: proceedings of the Satellite Symposium on Muscular Dystrophy Research 90, Venice, Italy, 14-15 September 1990, held in conjunction with the VIIth International Congress on Neuromuscul. Author: Satellite Symposium on Muscular Dystrophy Research 90 (1990: Venice, Italy); Year: 1991; Amsterdam; New York: Excerpta Medica; New York, NY, USA: Sole distributors for the USA and Canada, Elsevier Science Pub. Co., 1991; ISBN: 044481406X (alk. paper) http://www.amazon.com/exec/obidos/ASIN/044481406X/icongroupi nterna

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Myoblast transfer: gene therapy for muscular dystrophy. Author: Peter K. Law; Year: 1994; Austin: R.G. Landes; Boca Raton, FL: CRC Press [distributor], 1994; ISBN: 1879702762 (hard cover) http://www.amazon.com/exec/obidos/ASIN/1879702762/icongroupin terna

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Pathogenesis and therapy of Duchenne and Becker muscular dystrophy. Author: editors, Byron A. Kakulas, Frank L. Mastaglia; Year: 1990; New York: Raven Press, c1990; ISBN: 0881675970 http://www.amazon.com/exec/obidos/ASIN/0881675970/icongroupin terna

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Psychosocial aspects of muscular dystrophy and allied diseases: commitment to life, health, and function. Author: edited by Leon I. Charash ... [et al.]; with the editorial assistance of Lillian G. Kutscher; Year: 1983; Springfield, Ill., U.S.A.: Thomas, c1983; ISBN: 0398048118 http://www.amazon.com/exec/obidos/ASIN/0398048118/icongroupin terna

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Readings in muscular dystrophy. Author: Douglas H. Ruben, ed., Nancy R. Macciomei, ed; Year: 1986; New York: Longman, c1986; ISBN: 058228659X

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http://www.amazon.com/exec/obidos/ASIN/058228659X/icongroupi nterna ·

Research into the origin and treatment of muscular dystrophy: proceedings of a workshop held at "De Hooge Vuursche", Baarn, Holland, 24-27 February 1984. Author: editors, L.P. ten Kate, P.L. Pearson, A.M. Stadhouders; Year: 1984; Amsterdam; Princeton: Excerpta Medica, 1984; ISBN: 9021996715 http://www.amazon.com/exec/obidos/ASIN/9021996715/icongroupin terna

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Ventilators & muscular dystrophy. Author: by Nancy C. Schock and Agatha P. Colbert; Year: 1990; St. Louis, Mo.: Gazette International Networking Institute, 1990; ISBN: 0931301033 http://www.amazon.com/exec/obidos/ASIN/0931301033/icongroupin terna

Chapters on Muscular Dystrophy Frequently, muscular dystrophy will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with muscular dystrophy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and muscular dystrophy using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” By making these selections and typing in “muscular dystrophy” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The following is a typical result when searching for book chapters on muscular dystrophy: ·

Muscular Dystrophy: Duchenne Muscular Dystrophy, Becker Muscular Dystrophy Source: in Plumridge, D., et al., eds. Student with a Genetic Disorder: Educational Implications for Special Education Teachers and for Physical Therapists, Occupational Therapists, and Speech Pathologists. Springfield, IL: Charles C Thomas Publisher. 1993. p. 180-185. Contact: Available from Charles C Thomas Publisher. 2600 South First Street, Springfield, IL 62794-9265. (212) 789-8980. Fax (217) 789-9130. PRICE: $75.95 plus shipping and handling (cloth); $39.95 plus shipping and handling (paper). ISBN: 0398058393.


Summary: Both Duchenne and Becker muscular dystrophy are progressive muscle wasting conditions that primarily affect boys. This chapter on muscular dystrophy is from a text for special education teachers, physical therapists, occupational therapists, and speech pathologists on the educational implications of genetic disorders. Topics covered include the physical and characteristic features of the disorder, the genetics of the disorder, the cognitive and behavior profiles, the educational implications, physical therapy, occupational therapy, hearing and speech considerations, psychosocial issues, and prognosis. 5 references. ·

Myotonic Dystrophy: Steinert Muscular Dystrophy, Dytrophia Myotonica Source: in Plumridge, D., et al., eds. Student with a Genetic Disorder: Educational Implications for Special Education Teachers and for Physical Therapists, Occupational Therapists, and Speech Pathologists. Springfield, IL: Charles C Thomas Publisher. 1993. p. 186-191. Contact: Available from Charles C Thomas Publisher. 2600 South First Street, Springfield, IL 62794-9265. (217) 789-8980. Fax (217) 789-9130. PRICE: $75.95 plus shipping and handling (cloth); $39.95 plus shipping and handling (paper). ISBN: 0398058393. Summary: Myotonic dystrophy is a type of muscular dystrophy that affects other parts of the body in addition to muscles. This chapter on myotonic dystrophy is from a text for special education teachers, physical therapists, occupational therapists, and speech pathologists on the educational implications of genetic disorders. Topics covered include the physical and characteristic features of the disorder, the genetics of the disorder, the cognitive and behavior profiles, the educational implications, physical therapy, occupational therapy, hearing and speech considerations, psychosocial issues, and prognosis. 6 references.

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Neuromuscular Disorders Source: in Grundy, M.C.; Shaw, L.; and Hamilton, D.V. Illustrated Guide to Dental Care for the Medically Compromised Patient. St. Louis, MO: Mosby-Year Book, Inc. 1993. p. 87-88. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 432-1380; E-mail: [email protected]; http://www.mosby.com. PRICE: $24.95 plus shipping and handling. ISBN: 0815140223.

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Summary: This chapter, from an illustrated guide to dental care for medically compromised patients, discusses neuromuscular disorders. Topics covered include muscular dystrophy, myasthenia gravis, and Guillain-Barre syndrome. For each condition, the authors provide a brief description, the components of medical management, and suggestions for dental care.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to muscular dystrophy have been published that consolidate information across various sources. These too might be useful in gaining access to additional guidance on muscular dystrophy. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:27 ·

Sports, Anyone? Source: Alexandria, VA, Orthotics and Prosthetics National Office, 17 p., September 1994. Contact: Orthotics and Prosthetics National Office, 1650 King Street, Suite 500, Alexandria, VA 22314. (703) 836-7114. Summary: Sports, Anyone? gives detailed information on organizations that offer physical activities programs for individuals with disabilities. The National Handicapped Sports (NHS) and other U.S. Olympic Committee Disabled Sports Organizations offer training programs and conduct competitions that can give the disabled person the opportunity to compete in the Paralympic Games, which immediately follow the Olympics. Disabled Sports Organizations listed in the directory include the American Athletic Association of the Deaf (AAAD), the Dwarf Athletic Association of America (DAAA), the National Amputee Golf Association (NAGA), National Handicapped Sports (NHS), the United States Association of Blind Athletes (USABA), the United States Cerebral Palsy Athletic Association (USCPAA), the United States Les Autres Sports Association (USLASA) (which includes persons with such

You will need to limit your search to “Directories” and muscular dystrophy using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by”. For publication date, select “All Years”, select language and the format option “Directory”. By making these selections and typing in “muscular dystrophy” (or synonyms) into the “For these words:” box, you will only receive results on directories dealing with muscular dystrophy. You should check back periodically with this database as it is updated every three months.

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physical impairments as multiple sclerosis, muscular dystrophy, osteogenesis imperfecta, and other lesser-known disabilities), and Wheelchair Sports USA. Each entry includes address, telephone, and contact person information, eligibility criteria, a brief description of the organization, and the types of activities offered. The directory concludes with two inspirational essays, Rising to the Top and Essentials of Activity, which were written by disabled athletes, and provides information about the 1996 Paralympic Games in Atlanta, Georgia. ·

9Health Fair Referral Guide Source: Denver, CO, Nine Health Services, Inc., 216 p., 1994. Contact: Nine Health Services, Inc., 825 East Speer Boulevard, Suite 200, Denver, CO 80218. (303) 698-4455. Summary: 9Health Fair Referral Guide is a publication of Nine Health Services, Inc. in Denver, Colorado, and is primarily used as a resource guide by health professionals at 9Health Fairs across Colorado. The Guide was compiled as a general reference with an emphasis on agencies that serve individuals and families on a limited income. It does, however, have resources for all income levels. Each resource listed in the Referral Guide includes an address, phone number, available services and resources, and cost. Resources are listed in each of the following categories: Crisis and emergency numbers, acquired immune deficiency syndrome (AIDS), alopecia areata, Alzheimer's disease, arthritis, blood pressure screenings, cancer, cardiovascular, cerebral palsy, chiropractic, clinics, cystic fibrosis, dental care, dermatology, diabetes, disabled resources, eating disorders, epilepsy, general consumer information and education, government agencies, hearing, home health care, hospitals in metro Denver, immunizations, intestinal diseases, kidney disease, leukemia, living wills and related issues, lupus, medical societies, mental health, migrant health program, multiple sclerosis, muscular dystrophy, nutrition, orthodontics, ostomies, Parkinson's disease, physical therapy, podiatry, post-polio, prostate and testicular cancer, rehabilitation centers, respiratory diseases, runaways and shelters, safety, senior services, sexuality and family planning, sexually transmitted diseases, sickle cell anemia, shelter, smoking withdrawal and smokeless tobacco, social services agencies, speech and language, sports medicine, stress and grief, substance abuse (including alcohol and drug), suicide prevention, transplant resources, transportation, victim assistance, vision, and weight control. Resources are also listed for the following Colorado regions: Central and Mountain area, Eastern, Northern, Southern, and Western. Information numbers and referral services are also listed.

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Scientific Advisory Board, FSH Society, Inc Source: Lexington, MA: FacioScapuloHumeral Society, Inc. (FSH Society). 1995. [2 p.]. Contact: Available from FacioScapuloHumeral Society, Inc. (FSH Society). 3 Westwood Road, Lexington, MA 02173. (617) 860-0501. PRICE: Free. Summary: This directory lists the names, addresses and telephone numbers of the Scientific Advisory Board for the FacioScapuloHumeral Society, Inc. (FSH Society). The FSH Society, Inc. is a non-profit organization that addresses issues and needs specific to patients with facioscapulohumeral muscular dystrophy (FSHD).

General Home References In addition to references for muscular dystrophy, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · American College of Physicians Complete Home Medical Guide (with Interactive Human Anatomy CD-ROM) by David R. Goldmann (Editor), American College of Physicians; Hardcover - 1104 pages, Book & CD-Rom edition (1999), DK Publishing; ISBN: 0789444127; http://www.amazon.com/exec/obidos/ASIN/0789444127/icongroupinterna · The American Medical Association Guide to Home Caregiving by the American Medical Association (Editor); Paperback - 256 pages 1 edition (2001), John Wiley & Sons; ISBN: 0471414093; http://www.amazon.com/exec/obidos/ASIN/0471414093/icongroupinterna · Anatomica : The Complete Home Medical Reference by Peter Forrestal (Editor); Hardcover (2000), Book Sales; ISBN: 1740480309; http://www.amazon.com/exec/obidos/ASIN/1740480309/icongroupinterna · The HarperCollins Illustrated Medical Dictionary : The Complete Home Medical Dictionary by Ida G. Dox, et al; Paperback - 656 pages 4th edition (2001), Harper Resource; ISBN: 0062736469; http://www.amazon.com/exec/obidos/ASIN/0062736469/icongroupinterna · Mayo Clinic Guide to Self-Care: Answers for Everyday Health Problems by Philip Hagen, M.D. (Editor), et al; Paperback - 279 pages, 2nd edition (December 15, 1999), Kensington Publishing Corp.; ISBN: 0962786578; http://www.amazon.com/exec/obidos/ASIN/0962786578/icongroupinterna


· The Merck Manual of Medical Information : Home Edition (Merck Manual of Medical Information Home Edition (Trade Paper) by Robert Berkow (Editor), Mark H. Beers, M.D. (Editor); Paperback - 1536 pages (2000), Pocket Books; ISBN: 0671027263; http://www.amazon.com/exec/obidos/ASIN/0671027263/icongroupinterna

Vocabulary Builder Alopecia: Baldness; absence of the hair from skin areas where it normally is present. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Hemidesmosomes: An anchoring junction of the cell to a non-cellular substrate, similar in morphology to halves of desmosomes. They are composed of specialized areas of the plasma membrane where intermediate filaments bind on the cytoplasmic face to the transmembrane linkers, integrins, via intracellular attachment proteins, while the extracellular domain of the integrins binds to extracellular matrix proteins. [NIH] Immunization: The induction of immunity. [EU] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]

Podiatry: A specialty concerned with the diagnosis and treatment of foot disorders and injuries and anatomic defects of the foot. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the

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deep layer of the triangular ligament, and rests upon the rectum. [NIH] Thanatology: The study of the theory, philosophy, and doctrine of death. [NIH]

Multimedia 123

CHAPTER 7. MULTIMEDIA ON MUSCULAR DYSTROPHY Overview Information on muscular dystrophy can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on muscular dystrophy. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine. If you see an interesting item, visit your local medical library to check on the availability of the title.

Video Recordings Most diseases do not have a video dedicated to them. If they do, they are often rather technical in nature. An excellent source of multimedia information on muscular dystrophy is the Combined Health Information Database. You will need to limit your search to “video recording” and “muscular dystrophy” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” By making these selections and typing “muscular dystrophy” (or synonyms) into the “For these words:” box, you will only receive results on video productions. The following is a typical result when searching for video recordings on muscular dystrophy:


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Doctor is In: Speech Source: Princeton, NJ: Films for the Humanities and Sciences. 1991. (videocassette). Contact: Available from Films for the Humanities and Sciences, Inc. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5726 or (609) 275-1400; Fax (609) 275-3767. PRICE: $140.00 each; $75.00 (rental); plus shipping and handling. Summary: This videocassette is one in a series of programs that explain and explore major health concerns. This program on speech and speech disorders introduces a woman recovering from a stroke, a child with muscular dystrophy, a man who has had his larynx removed, a child who stutters, and an immigrant trying to lose her Polish accent. The program explores how men and women can use their voices effectively and describes what happens when one loses the voice. A featured expert is Dr. Robert Sataloff, Professor of Otolaryngology at Jefferson Medical College in Philadelphia, editor of 'The Journal of Voice', and an opera singer. Host, Jamie Guth, also speaks with speech pathologists and a person who stutters and is helping others cope with the problem. (AAM).

Bibliography: Multimedia on Muscular Dystrophy The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in muscular dystrophy (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on muscular dystrophy. For more information, follow the hyperlink indicated: ·

Congenital and inherited diseases. Source: Grover M. Hutchins; Year: 1978; Format: Slide; [New York]: Medcom, c1978

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Disorder of motility. Source: Wayne State University College of Medicine and CIBA Pharmaceutical Products, Inc.; produced by Rex Fleming; Year: 1969; Format: Motion picture; [Summit, N. J.]: CIBA; [Detroit: for loan and sale by Wayne State Univ., c196-?]

Multimedia 125

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Disorders of gait. Source: from the Department of Neurology, College of Physicians and Surgeons, Columbia University and the Neurological Institute; prepared by T.J. Putnam and E. Herz; Year: 1948; Format: Motion picture; United States: King's Crown Press, [1948]

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Duchenne's pseudohypertrophic muscular dystrophy. Source: authors, Lynette Chandler, Shari Freshman, Jeanne Fischer; produced by Division of Physical Therapy, Dept. of Rehabilitation Medicine and Health Sciences Learning Resources Center, University of; Year: 1981; Format: Slide; [Seattle, Wash.]: The Division, c1981

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External intercostal muscle biopsy. Source: Radio-TV-Film Bureau, Medical-TV-Cinematography Division, Arizona Health Sciences Center, University of Arizona; Year: 1976; Format: Videorecording; Tucson, Ariz.: Arizona Board of Regents: [for sale by Health Sciences Center, Biomedical Communications], c1976

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Gait and musculoskeletal disorders. Source: Wayne State University College of Medicine and CIBA Pharmaceutical Products, Inc.; produced by Rex Fleming; Year: 1969; Format: Motion picture; [Summit, N. J.]: CIBA; [Detroit: for loan and sale by Wayne State Univ., c196-?]

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Gemini inheritance. Source: [presented by] Filmakers Library, Inc.; [produced by Yorkshire Television]; Year: 1990; Format: Videorecording; [England]: Yorkshire Television, c1990

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Genetic counseling. Source: National Institute of Neurological and Communicative Disorders & Stroke; Year: 1978; Format: Videorecording; [Bethesda, Md.]: The Institute; [Atlanta: for loan by National Medical Audiovisual Center; Washington: for sale by National Audiovisual Center, 1978]

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Genetic discoveries, disorders, and mutations. Source: a presentation of Films for the Humanities and Sciences; [presented by] Animated Biomedical Productions; Year: 2000; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c2000

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Limb girdle dystrophy. Source: College of Medicine, Ohio State University; [produced by] Medical Audio-Visual and Television Center; Year: 1977; Format: Videorecording; Columbus, Ohio: The University: [for sale by its Health Services Audio-Visual and Television Center], c1977

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Medical research : the celebrity edge. Source: a presentation of Films for the Humanities & Sciences; Year: 1998; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c1998

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Medical terminology: orthopedic disorders and surgery. Source: AuVid, inc; Year: 1974; Format: Sound recording; [Garden Grove, Calif.]: Au-Vid, [1974]


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Mobility problems of children. Source: Medical Electronic Educational Services, in cooperation with Western Wisconsin Technical Institute; Year: 1975; Format: Filmstrip; LaCrosse, Wi.: The Institute, c1975

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Muscular dystrophy and related conditions : differential diagnosis. Source: Muscular Dystrophy Associations of America; produced by Sturgis-Grant Productions; Year: 1966; Format: Motion picture; New York: The Associations; [Atlanta: for loan by National Medical Audiovisual Center], 1966

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Muscular dystrophy, the race for the gene. Source: a BBC TV production for the Open University, in association with Coronet/MTI Film and Video; Year: 1987; Format: Videorecording; [London, England]: Open University, c1987

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Muscular dystrophy. Source: the American Academy of Orthopaedic Surgeons; Year: 1976; Format: Slide; [Chicago, Ill.]: The Academy, [1976]

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Muscular dystrophy. Source: Trainex Corporation; Year: 1973; Format: Videorecording; Garden Grove, Calif.: Trainex, c1973

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Muscular dystrophy. Source: Trainex Corporation; Year: 1973; Format: Filmstrip; Garden Grove, Calif: Trainex, c1973

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Muscular dystrophy. Source: Donald L. Schotland; Year: 1971; Format: Slide; [New York]: Medcom, c1971

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Muscular dystrophy. Source: a Films for the Humanities and Sciences presentation; a production of the Dartmouth-Hitchcock Medical Center; Year: 1990; Format: Videorecording; Princeton, N.J.: Film for the Humanities & Sciences, c1990

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Neuro-muscular disorders. Source: Hospital for Sick Children, Toronto; [produced by] Division of Instructional Media Services, Faculty of Medicine, University of Toronto; Year: 1975; Format: Motion picture; Toronto: The Division, 1975

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Orthopedic and habilitation aspects and prevention of severe deformity in children and adolescents with neuromuscular diseases. Source: National Institutes of Health, Public Health Service, Dept. of Health, Education, and Welfare; Year: 1976; Format: Videorecording; [Bethesda, Md.]: The Institutes; [Atlanta: for loan by National Medical Audiovisual Center; Washington: for sale by National Audiovisual Center, 1976]

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Practical aspects of genetic counseling. Source: Academy of Health Sciences, United States Army Medical Department; Year: 1973; Format: Videorecording; Fort Sam Houston, Tex.: The Academy: [for loan by its Health Sciences Media Division], 1973

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Progressive muscular atrophies, dystrophies, and allied conditions. Source: by S. Philip Goodhart and Benjamin Harris Balser; Year: 1944; Format: Motion picture; [United States: Neuropsychiatric Division, Montefiore Hospital, 1944]

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Recombinant DNA technology and prenatal diagnosis of genetic disease. Source: with Haig Kazazian, Corinne D. Boehm, and Virginia Corson; Year: 1987; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1987

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Respiratory failure in neuromuscular disease. Source: Bertrand J. Shapiro; Year: 1974; Format: Slide; New York: Medcom, c1974

Vocabulary Builder Gait: Manner or style of walking. [NIH] Intercostal: Situated between the ribs. [EU] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Motility: The ability to move spontaneously. [EU] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH]

Periodicals and News 129

CHAPTER 8. PERIODICALS AND NEWS ON MUSCULAR DYSTROPHY Overview Keeping up on the news relating to muscular dystrophy can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on muscular dystrophy. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover muscular dystrophy beyond and including those which are published by patient associations mentioned earlier. We will first focus on news services, and then on periodicals. News services, press releases, and newsletters generally use more accessible language, so if you do chose to subscribe to one of the more technical periodicals, make sure that it uses language you can easily follow.

News Services & Press Releases Well before articles show up in newsletters or the popular press, they may appear in the form of a press release or a public relations announcement. One of the simplest ways of tracking press releases on muscular dystrophy is to search the news wires. News wires are used by professional journalists, and have existed since the invention of the telegraph. Today, there are several major “wires” that are used by companies, universities, and other organizations to announce new medical breakthroughs. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing.


PR Newswire Perhaps the broadest of the wires is PR Newswire Association, Inc. To access this archive, simply go to http://www.prnewswire.com. Below the search box, select the option “The last 30 days.” In the search box, type “muscular dystrophy” or synonyms. The search results are shown by order of relevance. When reading these press releases, do not forget that the sponsor of the release may be a company or organization that is trying to sell a particular product or therapy. Their views, therefore, may be biased.

Reuters The Reuters' Medical News database can be very useful in exploring news archives relating to muscular dystrophy. While some of the listed articles are free to view, others can be purchased for a nominal fee. To access this archive, go to http://www.reutershealth.com/frame2/arch.html and search by “muscular dystrophy” (or synonyms). The following was recently listed in this archive for muscular dystrophy: ·

Mouse study shows enzyme helps muscular dystrophy Source: Reuters Health eLine Date: April 19, 2002 http://www.reuters.gov/archive/2002/04/19/eline/links/20020419elin 019.html

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Gene therapy studied for muscular dystrophy Source: Reuters Health eLine Date: December 12, 2001 http://www.reuters.gov/archive/2001/12/12/eline/links/20011212elin 004.html

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Axcell, Mount Sinai in Alzheimer's, muscular dystrophy protein research pact Source: Reuters Industry Breifing Date: November 15, 2001 http://www.reuters.gov/archive/2001/11/15/business/links/20011115 inds008.html

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House approves muscular dystrophy research push Source: Reuters Medical News Date: September 25, 2001 http://www.reuters.gov/archive/2001/09/25/professional/links/20010 925legi001.html


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House approves muscular dystrophy funding bill Source: Reuters Industry Breifing Date: September 25, 2001 http://www.reuters.gov/archive/2001/09/25/business/links/20010925 legi002.html

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Mini-protein restores muscle function in murine model of muscular dystrophy Source: Reuters Industry Breifing Date: September 19, 2001 http://www.reuters.gov/archive/2001/09/19/business/links/20010919 scie002.html

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Gene therapy fights muscular dystrophy in mice Source: Reuters Health eLine Date: September 19, 2001 http://www.reuters.gov/archive/2001/09/19/eline/links/20010919elin 005.html

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Genetic cause found for type of muscular dystrophy Source: Reuters Medical News Date: August 03, 2001 http://www.reuters.gov/archive/2001/08/03/professional/links/20010 803scie001.html

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Gene mutation linked to form of muscular dystrophy Source: Reuters Health eLine Date: August 02, 2001 http://www.reuters.gov/archive/2001/08/02/eline/links/20010802elin 010.html

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FDA pulls fast track status from muscular dystrophy study Source: Reuters Industry Breifing Date: May 01, 2001 http://www.reuters.gov/archive/2001/05/01/business/links/20010501 rglt006.html

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Key signaling mechanism could point to muscular dystrophy treatment Source: Reuters Medical News Date: April 27, 2001 http://www.reuters.gov/archive/2001/04/27/professional/links/20010 427scie002.html


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Benefit seen with long-term deflazacort for Duchenne muscular dystrophy Source: Reuters Industry Breifing Date: February 27, 2001 http://www.reuters.gov/archive/2001/02/27/business/links/20010227 clin007.html

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Muscular dystrophy gene therapy works in mice Source: Reuters Health eLine Date: February 23, 2001 http://www.reuters.gov/archive/2001/02/23/eline/links/20010223elin 024.html

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Muscle growth factor might treat age-related muscle wasting, muscular dystrophy Source: Reuters Industry Breifing Date: February 08, 2001 http://www.reuters.gov/archive/2001/02/08/business/links/20010208 scie002.html

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Verapamil prevents cardiomyopathy in mice with limb-girdle muscular dystrophy Source: Reuters Medical News Date: January 23, 2001 http://www.reuters.gov/archive/2001/01/23/professional/links/20010 123scie005.html

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Gene therapy for muscular dystrophy promising Source: Reuters Health eLine Date: November 30, 2000 http://www.reuters.gov/archive/2000/11/30/eline/links/20001130elin 006.html

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Repeats in muscular dystrophy gene responsible for disease in mice Source: Reuters Industry Breifing Date: September 11, 2000 http://www.reuters.gov/archive/2000/09/11/business/links/20000911 scie002.html

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Unusual mutation linked to muscular dystrophy Source: Reuters Health eLine Date: September 07, 2000 http://www.reuters.gov/archive/2000/09/07/eline/links/20000907elin 014.html


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Chimeric oligonucleotide repairs mutation in dog model of muscular dystrophy Source: Reuters Medical News Date: June 02, 2000 http://www.reuters.gov/archive/2000/06/02/professional/links/20000 602scie003.html

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Gene for novel sarcomeric protein may be involved in muscular dystrophy Source: Reuters Medical News Date: December 17, 1999 http://www.reuters.gov/archive/1999/12/17/professional/links/19991 217scie005.html

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Muscular dystrophy gene linked to heart disorder Source: Reuters Health eLine Date: December 02, 1999 http://www.reuters.gov/archive/1999/12/02/eline/links/19991202elin 005.html

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Stem cell transplantation restores dystrophin in mouse muscular dystrophy model Source: Reuters Medical News Date: September 23, 1999 http://www.reuters.gov/archive/1999/09/23/professional/links/19990 923scie004.html

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Bone marrow transplantation for muscular dystrophy Source: Reuters Health eLine Date: September 22, 1999 http://www.reuters.gov/archive/1999/09/22/eline/links/19990922elin 011.html

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Loss of nitric-oxide signaling linked to etiology of muscular dystrophy Source: Reuters Medical News Date: August 16, 1999 http://www.reuters.gov/archive/1999/08/16/professional/links/19990 816scie002.html

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New clue to muscular dystrophy Source: Reuters Health eLine Date: December 07, 1998 http://www.reuters.gov/archive/1998/12/07/eline/links/19981207elin 011.html


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Gene associated with two types of muscular dystrophy identified Source: Reuters Medical News Date: September 03, 1998 http://www.reuters.gov/archive/1998/09/03/professional/links/19980 903scie001.html

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Utrophin Transgene Corrects Clinical Signs Of Muscular Dystrophy In Mouse Model Of The Disease Source: Reuters Medical News Date: April 28, 1998 http://www.reuters.gov/archive/1998/04/28/professional/links/19980 428drgd002.html

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Duchenne Muscular Dystrophy: Noninvasive Respiratory Protocol Effective Source: Reuters Medical News Date: October 31, 1997 http://www.reuters.gov/archive/1997/10/31/professional/links/19971 031clin007.html

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Duchenne Muscular Dystrophy: A Better Mouse Model Built Source: Reuters Medical News Date: August 25, 1997 http://www.reuters.gov/archive/1997/08/25/professional/links/19970 825scie001.html

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New Protein May Fight Muscular Dystrophy Source: Reuters Health eLine Date: December 04, 1996 http://www.reuters.gov/archive/1996/12/04/eline/links/19961204elin 004.html

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Upregulation Of Utrophin Relieves Muscular Dystrophy In Mice Source: Reuters Medical News Date: November 28, 1996 http://www.reuters.gov/archive/1996/11/28/professional/links/19961 128scie001.html

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Gene Therapy For Muscular Dystrophy Source: Reuters Health eLine Date: September 04, 1996 http://www.reuters.gov/archive/1996/09/04/eline/links/19960904elin 010.html


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