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`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`MULTIPLE
`SCLEROSIS
`
`CURRENT STATUS AND
`
`STRATEGIES FOR THE FUTURE
`
`Janet E. Joy and Richard B. Johnston, Jr., Editors
`
`Committee on Multiple Sclerosis:
`Current Status and Strategies for the Future
`
`Board on Neuroscience and Behavioral Health
`
`INSTITUTE OF MEDICINE
`
`NATIONAL ACADEMY PRESS
`Washington, D.C.
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`NATIONAL ACADEMY PRESS« 2101 Constitution Avenue, N.W. * Washington, DC 20418
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`NOTICE: The project that is the subject of this report was approved by the Governing Board of the
`National Research Council, whose members are drawn from the councils of the National Academy of
`Sciences, the National Academy of Engineering, and the Institute of Medicine. The members ofthe
`committee responsible for the report were chosen for their special competencies and with regard for
`appropriate balance.
`
`Support for this project was provided by the National Multiple Sclerosis Society. The views
`presented in this report are those of the Institute of Medicine Committee on Multiple Sclerosis:
`Current Status and Strategies for the Future and are not necessarily those of the funding agencies.
`
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`For more information aboutthe Institute of Medicine, visit the IOM home pageat:
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`Library of Congress Cataloging-in-Publication Data
`
`Multiple sclerosis : current status and strategies for the future /
`Janet E. Joy and Richard B. Johnston, Jr., editors.
`p.3 cm.
`Includes bibliographical references and index.
`ISBN 0-309-07285-9 (hardcover)
`1. Multiple sclerosis.
`[DNLM: |. Multiple Sclerosis—therapy. 2. Multiple
`Sclerosis—physiopathology. 3. Research. WL 360 M956378 2001]
`Janet E. Janet Elizabeth), 1953- II. Johnston, Richard B., 1935-
`RC377 .M8455 2001
`616.8’34—de21
`
`2001002431
`
`I. Joy,
`
`Copyright 2001 by the National Academy of Sciences. All rights reserved.
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`Printed in the United States of America.
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`Copyright National Academy of Sciences. All rights reserved.
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`Multiple Sclerosis: Current Status and Strategies for the Future
`
`“Knowing is not enough; we must apply.
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`INSTITUTE OF MEDICINE
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`Shaping the Future for Health
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`Copyright National Academy of Sciences. All rights reserved.
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`Multiple Sclerosis: Current Status and Strategies for the Future
`
`| pul NAI |¢ IN, WL A\WLAAL
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`A i
`_ ae h
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`National Academy of Sciences
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`The National Academy of Sciences is a private, nonprofit, self-perpetuating society of
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`Copyright National Academy of Sciences. All rights reserved.
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`Multiple Sclerosis: Current Status and Strategies for the Future
`
`COMMITTEE ON MULTIPLE SCLEROSIS: CURRENT STATUS AND
`STRATEGIES FOR THE FUTURE
`
`Ricuarp B. JoHNsron, JR. (Chair), Professor of Pediatrics, National Jewish
`Medical and Research Center, University of Colorado School of Medicine
`JAcK P. ANTEL, Professor of Neurology and Neurosurgery, Montreal
`Neurological Hospital and Institute, McGill University, Quebec, Canada
`SAMUEL BropeEr, Executive Vice President for Medical Affairs, Celera
`Genomics, Rockville, Maryland
`JESSE M. Ceparsaum,Vice President of Clinical Affairs, Regeneron
`Pharmaceuticals, Tarrytown, New York
`Patricia K. Coy.e, Professor of Neurology, State University of New York,
`Stony Brook
`STEPHEN L. Hauser, Professor of Neurology, University of California, San
`Francisco School of Medicine
`Lisa I. Jezzoni, Professor of Medicine, Harvard Medical School, Beth Israel
`Deaconess Medical Center, Boston, Massachusetts
`SUZANNE T. ILpstap, Director of Institute for Cellular Therapeutics, University
`of Louisville, Kentucky
`SHARON L. JULIANO, Professor of Anatomy and Cell Biology and
`Neurosciences Program, Uniformed Services University of the Health
`Sciences, Bethesda, Maryland
`DonaL. Price, Professor of Pathology, Neurology and Neuroscience, Johns
`Hopkins University School of Medicine, Baltimore, Maryland
`Raymonp P. Roos, Professor of Neurology, University of Chicago, Illinois
`ALAN J. THompson,Professor of Neurology, University College, London,
`England
`STEPHEN G. WAXMAN,Professor of Neurology, Yale Medical School, New
`Haven, Connecticut
`HaArTMUT WEKERLE,Director, Max-Planck-Institut fur Neurobiologie, Planegg-
`Martinsreid, Germany
`
`StudyStaff
`
`JANET E. Joy, Study Director
`Joun A. ROCKWELL, Research Assistant
`AMELIA B. Marais, Project Assistant
`Linpa Leonarp, Administrative Assistant (until 9/2000)
`Lora K. Taytor, Administrative Assistant (from 9/2000)
`Terry C. PeLLMar, Board Director
`Car_os GABRIEL, Financial Associate
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`BOARD ON NEUROSCIENCE AND BEHAVIORAL HEALTH
`
`ANN M. GraysiEL (Chair), Massachusetts Institute of Technology, Cambridge
`KeEennetu B. WELLS (Vice-Chair), Neuropsychiatric Institute, University of
`California, Los Angeles
`Nancy E. ADLER, University of California, San Francisco
`Ricuarp J. BonntE, University ot Virginia School ot Law, Charlottesville
`WiiuiaM E. Bunney, University of California, Irvine
`Ricuarp G. Frank, Harvard Medical School, Boston, Massachusetts
`JEROME KaGan, Harvard University, Cambridge, Massachusetts
`HERBERT D. Keser, Columbia University and New York State Psychiatric
`Institute, New York, New York
`BEVERLY B. Lone, World Federation for Mental Health, Atlanta, Georgia
`KATHLEEN R. MERIKANGAS, Yale University, New Haven, Connecticut
`STEVEN M. Mirin, American Psychiatric Association, Washington, D.C.
`STEVEN M. Paut, Lilly Research Laboratories, Indianapolis, Indiana
`Davi Reiss, George Washington University Medical Center, Washington, D.C.
`RuonpA J. RoBinson-BEALE, Blue Cross/Blue Shield of Michigan, Southfield
`STANLEY J. Watson, University of Michigan, Ann Arbor
`STEPHEN G. WAXMAN, Yale Medical School, New Haven, Connecticut
`Nancy S. WEXLER, Columbia University, New York, New York
`ANNE B. YounG, Massachusetts General Hospital, Boston
`
`Vi
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`Preface
`
`Multiple sclerosis (MS) is not a new disease. Its effects on the brain were
`described in the 1830s, and it was identified as a distinct clinical entity in the
`1860s. In fact, writings from the Middle Ages appear to describe individuals with
`this condition. MS is the most commonneurological disorder of young adults;
`there are approximately 350,000 people with MS in the United States and an
`estimated 2 million patients worldwide.
`Research on the disorder has been energetic over recent decades. In 1996, the
`U.S. National Institutes of Health (NIH) spent almost $83 million on MS re-
`search. This sum exceeded the NIH expenditure that year on asthma, tuberculo-
`sis, or cervical cancer. MS has not been neglected by researchers in this country
`or worldwide.
`As a result, important progress has been made in defining the pathologic
`changes of MS, in using new imaging techniques for evaluation, and in develop-
`ing treatments that can modify its course. Yet, despite concerted effort on the part
`of many good researchers, the fundamental elements of MSarestill not under-
`stood, and the path toward consistently preventing its progression or curing it
`remains obscure. For example, we do not know what causes MS to appear in one
`person and not another. We do not know whatrole genes play. We have known
`for decades that MS has a widely variable clinical expression and unpredictable
`course, but do the variations reflect different causative agents or different re-
`sponses to the same basic cause? Most investigators consider MS to be an au-
`toimmunedisease, but what incites the autoimmune response—a change in the
`cells of the nervous system so that they appear foreign or a microbial agent that
`mimics a cell component? Whyis it approximately twice as common in women
`
`Vil
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`viii
`
`PREFACE
`
`as in men? How can we mosteffectively relieve the various troubling symptoms
`of MSsuch aspain and fatigue? How can wehelp people with MS adaptto the
`disease andlive their lives to the fullest level possible?
`The National Multiple Sclerosis Society was founded in 1946 to address
`these and other questions about MS. Its mission is simple and forthright: “To end
`the devastating effects of multiple sclerosis.” Through the efforts of its 650,000
`membersandstaff, it has made extraordinary contributions to understanding MS
`by a series of highly imaginative programs in research and patient services,
`including almost $300 million in research grants. The report that you see hereis
`the result of a request from the Society to the Institute of Medicine (IOM) for
`guidance in developing a strategic plan to direct future investments in MS re-
`search.
`The multidisciplinary committee convened by the IOM in responseto this
`request was charged to review current knowledgeof all aspects of MS from cells
`to symptoms; to identify techniques, resources, and innovations used outside the
`field that might be applied to the MS challenge; and to recommendstrategiesthat
`might push MSresearch forward mosteffectively.
`To address its charge, the committee, with the support of IOM staff, re-
`viewed the scientific literature related to all aspects of MS and received input
`from 45 outside consultants: 9 of these wrote state-of-the-art commentaries on
`symptom management, some told us what they needed most as MSpatients, and
`17 described the newest science during three workshops. Most of the workshop
`participants were not primarily involved in MS research or with MSpatients but
`agreed to brainstorm with us about how the best of their disciplines might be
`applied to MS. Weclearly could not have accomplished our work without the
`help of these consultants, and theirlisting in the Acknowledgments badly under-
`states ourgratitude. Finally, the committee recognizes with the deepest apprecia-
`tion the support given by the extraordinary staff assigned to us by the IOM—
`Janet Joy, John Rockwell, Amelia Mathis, and Terry Pellmar. In particular, Janet
`Joy, study director and neuroscientist by training, with intelligence, humor, and
`an exceptionalintensity of commitment, inspired and guided us to the completion
`of our task.
`
`Richard B. Johnston, Jr., M.D.
`Chair
`
`Copyright National Academyof Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`Acknowledgments
`
`People live with multiple sclerosis (MS) for decades, making it a disease of
`selves as well as cells. The committee’s assessment of the current status of
`progress against MS thus entailed a review from biomedical perspectives, as well
`as from psychological and social perspectives. This massive undertaking could
`not have been accomplished without the help of an array of experts as multi-
`faceted as the disease itself. The committee is deeply indebted to these many
`people for their valuable contributions.
`The following people wrote invaluable background papers for the commit-
`tee: Dedra Buchwald (fatigue), Howard Fields (pain), Robert W. Hamill (bladder
`and bowelcontrol), David E. Krebs(assistive technology), T. Jock Murray (cog-
`nitive impairment), Peggy Neufeld (assistive technology), Trevor Owens (ge-
`netic animal models), Robert G. Robinson (depression and brain injury), William
`Z. Rymer(spasticity and weakness), and Marca Sipski (sexual function).
`Another group presented a series of excellent talks on new approaches to MS
`research at workshops for the committee. This group includes Mindy Aisen,
`Michael Conneally, Scott E. Fraser, Chien Ho, Ole Isacson, Elliott D. Kieff,
`Jeffery Kocsis, Henry McFarland, Deborah Miller, Rhona Mirsky, Marc
`Peschanski, John C. Roder, Jay Siegel, Joy Snider, Lawrence Steinman, Barbara
`Vickrey, and Michael Weinrich. (Topics are listed individually in Appendix C.)
`The following people provided technical comments on draft sections of the
`report: Robert Burke, Mary Horwitz, Peggy Neufeld, John Roder, and Richard
`Rudick. Still others served as technical consultants either in meetings with the
`committee, sharing unpublished reports, or in consultations with Institute of Medi-
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`x
`
`ACKNOWLEDGMENTS
`
`cine (IOM)staff. This group includes Elaine Collier, Gary Karp, Lorna Layward,
`Ian McDonald, Sarah Minden, Audrey Penn, and Albert van der Pol.
`All of these people gave generously oftheir time and made a tremendous and
`much appreciated contribution to the breadth and depth ofthis report.
`Stephen Reingold, Vice President of Scientific Programs, and Nicholas
`LaRocca, Director of Health Care Delivery and Policy Research, at the National
`Multiple Sclerosis Society were indispensable to the committee’s efforts. They
`provided the committee with volumes of background material and fielded an
`endless stream of inquiries from IOM staff. They were unfailingly quick to reply
`to queries and providedstores of information.
`Miriam Davis and Jane Durch provided substantive editing for sections of
`the report, Amy Fluet wrote material for several of the explanatory boxes in the
`report, and Florence Poillon edited the uncorrected proofs. Each of them greatly
`enhancedthe readability of the report and weare grateful for their excellent work.
`This report has been reviewed in draft form by individuals chosen for their
`diverse perspectives andtechnical expertise, in accordance with procedures ap-
`proved by the National Research Council’s Report Review Committee. The pur-
`pose of this independent review is to provide candid and critical comments that
`will assist the institution in making the published report as sound as possible and
`to ensure that the report meets institutional standards for objectivity, evidence,
`and responsiveness to the study charge. The review comments and draft manu-
`script remain confidential to protect the integrity of the deliberative process. We
`wish to thank the following individuals for their participation in the review ofthis
`report:
`
`Fred Barkhof, Diagnostic Radiology, Vrije Universiteit Hospital, Amsterdam,
`Netherlands
`George Ebers, Professor, Department of Clinical Neurology, Oxford
`University
`Jill S. Fischer, Director, Psychology Program (1985-2000), Mellen Center for
`MS Treatment and Research Cleveland Clinic
`Zach W.Hall, Vice Chancellor, Office of Research, University of California,
`San Francisco
`Charles A. Janeway, Jr., Department of Immunobiology, Yale School of
`Medicine
`Alan M. Jette, Dean, Sargent College of Health and Rehabilitation Services,
`Boston University
`Jurg Kesselring, Professor and Head, Department of Rehabilitation Centre,
`Valens, Switzerland
`Samuel K. Ludwin, Professor, Pathology Department, Queens University,
`Ontario, Canada
`Robert H. Miller, Associate Professor, Case Western Reserve University
`School of Medicine
`
`Copyright National Academyof Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`ACKNOWLEDGMENTS
`
`xi
`
`Mary Beth Moncrief, Manager, Associate National Scientific Program
`Juvenile Diabetes Foundation International
`John Newsom-Davis, Professor, Clinical Neurology, University of Oxford
`Michael B.A. Oldstone, Professor, Department of Neuropharmacology,
`Division of Virology, The Scripps Research Institute
`Jerry Wolinsky, Professor, Department of Neurology, University of Texas,
`Houston Medical Center Health Science Center
`
`Although the individuals listed above have provided constructive comments
`and suggestions, they were not asked to endorse the conclusions or recommenda-
`tions nor did they see the final draft of the report before its release. The review of
`this report was overseen by Joseph B. Martin, Dean, Harvard Medical School and
`Floyd R. Bloom, Chair, Department of Neuropharmacology,
`the Scripps Re-
`search Institute, who were responsible for making certain that an independent
`examination of this report was carried out in accordance with institutional proce-
`dures andthat all review comments were carefully considered. Responsibility for
`the final content of this report rests entirely with the Committee on Multiple
`Sclerosis: Current Status and Strategies for the Future and the Institute of Medi-
`cine.
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`Contents
`
`EXECUTIVE SUMMARY (Sige ceeie cesses eee eek ee eae ewe e eve ll
`
`1
`
`INTRODUCTION tiiwseeeeeinree I
`The U.S. National Multiple Sclerosis Society, 19
`Recent Advances in MS, 21
`Origin of the Study, 21
`Previous Reviews of MS Research Programs, 22
`The IOM Committee and Its Mandate, 24
`How the Committee Carried Out its Task, 26
`Organization of the Report, 26
`References, 27
`
`CLINICAL AND BIOLOGICAL FEATURES ...........200000: 29
`The Clinical Picture: Symptoms, Disease Course, Variation,
`and Diagnosis, 29
`Underlying Disease Mechanisms, 54
`Animal Models of MS, 90
`References, 104
`
`CHARACTERISTICS AND MANAGEMENT OF
`MAJOR SYMPTOMS eeseusiaweewece enue 115
`Cognitive Impairment, 115
`Depression, 120
`Spasticity and Weakness, 128
`
`XU
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`xiv
`
`CONTENTS
`
`Ataxia and Tremor, 138
`Bladder and Bowel Dysfunction, 140
`Visual Disturbances, 148
`Fatigue, 149
`Sexual Dysfunction, 155
`Pain, 158
`References, 166
`
`4 DISEASE MANAGEMENT AND MEASUREMENT........... 177
`Living with MS, 178
`Measuring Functional Status and Quality of Life, 193
`Assistance, 205
`Information and Communication, 216
`Health Care, 221
`References, 229
`
`5
`
`6
`
`STRATEGIES FOR FUTURE RESEARCH ON
`DISEASE. MECHANISMS 334303eee 241
`Technologies and Research Strategies, 267
`References, 272
`
`FUTURE STRATEGIES FOR THERAPIES ........20:22005: Zat
`Strategies for Disease Modification, 278
`Challenges in MS Clinical Trials, 298
`Shared Resources, 312
`References, 318
`
`7 BUILDING AND SUPPORTING THE RESEARCH
`ENTERPRISE suveswinsiiecneweeS $25
`Research Funding, 325
`Human Resources, 333
`Infrastructure, 339
`Clinical Trials, 340
`Biotechnology and Pharmaceutical Firms, 341
`Health Care Research, 343
`Role of Voluntary Health Organizations, 344
`References, 346
`
`8 RECOMMENDATIONS so siebiee te is ee edie cede ceeeeenseess 347
`Etiology and Pathogenesis, 348
`Tools for Research and Diagnosis, 355
`Therapeutics, 358
`
`Copyright National Academyof Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`CONTENTS
`
`XV
`
`Health Status and Quality of Life, 361
`Research Enterprise, 363
`References, 367
`
`TZTHoOAWS>
`
`APPENDIXES
`Committee and Staff Biographies, 371
`List of Expert Consultants, 377
`Workshop Agendas, 379
`Kurtzke’s Expanded Disability Status Scale, 385
`Drugs Usedin the Treatment of MS, 387
`U.S. Social Security Administration’s Criteria for Qualifying as
`Disabled from MS, 401
`Treatments That Have Been Claimed to Be of Benefit in MS, 405
`
`a)
`
`INDEX sees eS PRESSES ee BINS See awe 413
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`Copyright National Academyof Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`List of Tables and Figures
`
`TABLES
`
`Varieties of MS, 30
`Initial Signs and Symptoms of MS, 32
`Prognostic Relapse Indicators, 34
`Information Provided by Neuroimaging, 38
`Proposed CSF Disease Markers in MS, 44
`Poser Diagnostic Criteria for MS, 46
`MRICriteria for Definite MS, 46
`Evoked Potentials as a Diagnostic Tool in MS, 47
`Disease-Modifying Therapies for Relapsing MS, 49
`Clinical Pathological Correlations in Common Syndromes of MS, 62
`Selected Diseases That Are Believed to Be Autoimmune Based, 69
`Possible Autoantigens in MS, 71
`CNS Demyelinating Diseases That Resemble MS, 85
`Koch’s Postulate on Causations of Disease by a Pathogen, 88
`Agents Isolated or Implicated in the Etiology of MS, 89
`Animal Models of MS, 91
`Comparison Between Multiple Sclerosis and EAE, 92
`Animal Viruses That Induce Demyelination, 96
`
`Medications Used to Treat Depression, 124
`Depression and Beta-Interferon, 126
`Medications Used to Treat Spasticity, 134
`Indications of Bladder Dysfunction, 141
`
`XVIL
`
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`
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`
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`
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`
`3.2
`
`3.3
`
`3.4
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`LIST OF TABLES AND FIGURES
`
`Medications Used to Treat Bladder and Bowel Dysfunction, 144
`Medications Used to Treat Optic Neuritis and Abnormal Eye
`Movements, 150
`Medications Used to Treat Fatigue, 154
`Neurological Pathways That Control Sexual Response in Men and
`Women, 157
`Medications Used to Treat Erectile Dysfunction, 159
`
`Hypothetical Results of a Clinical Trial, 262
`
`MRI Outcomesfor Clinical Trials, 310
`
`Research Budgets of Selected Health Organizations in 1998, 329
`
`FIGURES
`
`MSdistribution map, 18
`The nerve fiber in multiple sclerosis, 19
`
`Spectrum of disease course, 31
`Areas of the CNSaffected by MS, 32
`MRIscans of the brain, 37
`Oligodendrocyte making myelin, 55
`Pathogenesis, 57
`Axonal transection and degeneration, 59
`Possible mechanisms of demyelination, 61
`The blood-brain barrier, 63
`Interactions between major cell components of the immune system, 68
`Possible mechanism of viral etiology, 70
`
`Functions controlled by nerves at different levels of the spine, 129
`
`Demyelination and axonal degeneration in multiple sclerosis, 242
`Possible role of AMPA/kainate receptors on neuronsand glia, 244
`
`Lineage of neural stem cells, 294
`
`Relationship between NIH disease-specific research funding, 327
`Summary of publications in general medical journals, 328
`Summary of publications in neurology journals, 330
`Ph.D and postdoctoral fellowship trends, 335
`Trends in postdoctoral fellowship applications, 337
`
`XVILL
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`74
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`Executive Summary
`
`Multiple sclerosis (MS) is a complex disease that has been much more
`difficult to cure than was expected when the National Multiple Sclerosis Society
`(the MS Society) was founded in 1946 by Sylvia Lawry “to end the devastating
`effects of multiple sclerosis.” Yet optimism is possibly greater than it has ever
`been since those early years, in large part due to the developmentof the first
`treatments that can slow the progress of MS. Services for people with MS have
`also improved. “Diagnose and adios,” Labe Scheinberg’s famously disparaging
`quote aboutthe options available to MS neurologists in the 1970s, no longer rings
`true. Nor does the advice to young researchers that “if you want to ruin your
`career, go into MS.” Muchhas changedsince 1946. Still, no cause or cure for MS
`has been found. It remains a mysterious disease with no known pathogen or even
`known determinants of its severity and course.
`MSis not alone in this regard. Neurological diseases are among the most
`difficult to study, and although beneficial therapies have been developed in the
`last decades for Parkinson’s disease, Alzheimer’s disease, and epilepsy, there is
`still no cure for any of the degenerative neurological diseases. Advances on key
`fronts, such as improved ability to create images of the living brain and spinal
`cord, new understanding of the brain’s capacity for repair, and an overall acceler-
`ated pace of new discoveries about the cellular machinery of the brain, have
`renewed the optimism of many investigators about the possibility of developing
`effective therapeutic strategies for MS patients. New therapeutic strategies, such
`as gene therapy, stem cell transplantation, and neuroprotection strategies, rising
`on the horizon have emerged from recent advances in these areas.
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`2
`
`MULTIPLE SCLEROSIS
`
`Overthe years, the specific targets of MS research have been refocused and
`revised. The MS Society has reconsidered and remained committed to its focus
`on research. At the sametime, the scope of research topics has expanded, as have
`perspectives of the Society’s role. Although MSresearch hastraditionally been
`conducted on behalf of patients who remained in the background, now—to a
`small, but increasing degree—patient perspectives have stimulated new areas of
`research. New disciplines have emerged. Health care policy, functional status
`measurement, and quality-of-life assessment are all relatively new areas of re-
`search and are critically important for improving the lives of people with MS.
`The spectrum of current MS research ranges from strategies to develop treat-
`ments that impede the disease process, to treatments for specific symptoms, to
`research aimed at promoting successful adaptationstothe illness, including opti-
`mizing the abilities of people with MSto function in their daily lives.
`In December 1998, the National Multiple Sclerosis Society asked the Insti-
`tute of Medicine to undertake a strategic review of MS research on its behalf.
`This report presents the research strategies and programs that the committee
`believes are likely to be the most productive and most important in the near
`future. Throughout the study, the committee sought to identify windowsof op-
`portunity for research, such as those created by new discoveries aboutthe self-
`repair mechanisms of the brain or new disease-specific changes in gene activa-
`tion. The committee also soughtto identify research needs where the windowsof
`opportunity are less transparent, such as the development of evidence-based ap-
`proaches to address varied information needs of people with MSandto treat the
`fatigue and pain that so often accompany MS. Ideasfor the future are built on the
`review of current knowledge and gaps in the biomedical and social science of
`MS. The intended audience of this report includes the architects and developers
`of MSresearch programs, as well as people with MSandtheir families who want
`to learn whatis currently known about MS and what mightlie ahead.
`The report covers three broad areas: (1) biomedical aspects of the disease,
`causes, course, and treatments (Chapters 2, 5, and 6); (2) adaptation and manage-
`ment (combination of medical, technological, and psychosocial aspects) (Chap-
`ters 3 and 4); and finally, (3) proposals for research managers to facilitate re-
`search progress (Chapter 7).
`
`DisEASE CAUSES, COURSE AND TREATMENTS
`
`The ultimate goal of research in MSis the developmentof interventions that
`can improve the lives of those living with MS and can prevent or cure MS.
`However, understanding of the MS disease processis not yet sufficient to predict
`which therapeutic strategies will be most effective. Although the new disease-
`modifying drugs are a major leap forward,it is important to rememberthat they
`are not a cure, nor are they effective for all patients. The recommendations
`
`Copyright National Academy of Sciences. All rights reserved.
`
`

`

`Multiple Sclerosis: Current Status and Strategies for the Future
`
`EXECUTIVE SUMMARY
`
`3
`
`described below summarize the committee’s conclusions about which directions
`appear most likely to provide the fundamental knowledge that can lead to the
`developmentof effective therapies (see Box 1 for s