WHO? WHY? HOW? Searching for the Cause of Multiple Sclerosis NORTH AMERICAN EDUCATION PROGRAM 2010 WHO? WHY? The National Multiple Sclerosis Society is a collective H O of passionate individuals, moving together to create a W ? world free of MS. Searching for the Cause of Multiple Sclerosis nationalMSsociety.org +1 800 344 4867 Published in partnership with: Our mission is to be a leader in finding a cure for multiple sclerosis and enabling people affected by MS to enhance their quality of life. mssociety.ca +1 800 268 7582 © 2010 National Multiple Sclerosis Society © 2010 Multiple Sclerosis Society of Canada ON THE COVER: Kim (left), diagnosed in 1986 AJ (middle), diagnosed in 2000 Beverly (right), diagnosed in 2001 TABLE OF CONTENTS Acknowledgements .......................................................... 3 Program Staff ................................................................. 4 Preface ......................................................................... 5 Program Overview .......................................................... 6 Program Presenters .......................................................... 7 Program Biographies ........................................................ 8 What is the Cause of MS? ................................................ 19 The Role of Genetics in the Development of Multiple Sclerosis ..................................... 21 Genetic Susceptibility Among Family Members of People with MS ................................... 22 New Techniques Help Pinpoint Genetic Factors ..................... 23 Looking for DNA Markers .............................................. 23 Novel Genetic Variations ............................................... 25 Implications for People with MS ....................................... 25 Epidemiology: Who Develops MS? .................................... 26 Observations From Epidemiologic Studies ........................... 27 Recent Research Projects Related to Epidemiology and Possible Infectious Triggers of MS ................................ 27 Searching for the Cause of MS | 1 Environmental Factors & Multiple Sclerosis ......................... 29 Geography & Migration Patterns ...................................... 30 ACKNOWLEDGEMENTS Vitamin D & Sunlight ................................................... 31 Smoking .................................................................. 32 The National Multiple Sclerosis Society and the Multiple Sclerosis Toxic Substances ........................................................ 32 Hormones ................................................................ 33 Society of Canada wish to acknowledge the generous support of Tetanus Vaccine .......................................................... 34 Bayer HealthCare Pharmaceuticals, Biogen Idec, Genentech, Clusters & Epidemics .................................................... 34 Genzyme Corporation, and Teva Neuroscience, Inc. for the 2010 Evidence for an Infectious Cause of MS .............................. 35 North American Education Program — Who? Why? How? — The Epstein-Barr Virus (EBV) .......................................... 37 Searching for the Cause of MS. Non-Specific Immune Reactions in MS ............................... 38 The Role of Immunology in Multiple Sclerosis ...................... 39 Research Directed at the Role of the Immune System in MS ........ 40 The Roles of T-cells in Multiple Sclerosis .............................. 41 Chronic Cerebrospinal Venous Insufficiency (CCSVI): A Possible Factor in the Development of Multiple Sclerosis? ..... 42 Summary ..................................................................... 44 Glossary ...................................................................... 45 2 | Who? Why? How? Searching for the Cause of MS | 3 PROgrAM STAFF prEFACE JOHN AdEN Welcome to the 2010–2011 North American Education Program. Senior Manager, Program Development, National MS Society This program continues the successful collaboration between the CAthY CARLSON Senior Director, Research Information National MS Society in the United States and the MS Society of National MS Society Canada to provide the latest information about research and ROSALIND KALB, PhD disease management in multiple sclerosis to thousands of people Vice President, Professional Resource Center, National MS Society on our continent and around the world. NANCY LAW, LSW Executive Vice President, Programs and Services Department National MS Society This year, thanks to generous helping us to bring this program sponsorship from Bayer Health- to you. We are delighted that PAtriCIA A. O’LOONEY, PhD care Pharmaceuticals, Biogen you have chosen to participate Idec, Genentech, Genzyme Vice President of Biomedical Research, National MS Society in our program and hope that Corporation, and Teva Neuro- you find it interesting and science, Inc., our program will DIANA M. SCHNEidER, PhD, EditOR exciting. Together, we will be focus on finding the cause of MS. learning about how scientists are Consultant, National MS Society You will learn about theories — searching for the cause of MS past and present — and what — research that could some- the future may hold. day lead to a world free of MS. On behalf of our organizations We look forward to sharing this and the program sponsors, we program with you. wish to express our appreciation NANCY LAW to our researchers for taking the Executive Vice President time to speak with us and for Programs & Services Department letting us into their labs. In National MS Society addition, we want to thank the staff and volunteers of the JON TEMME National MS Society and MS Senior Vice President, Research & Society of Canada chapters for Programs, MS Society of Canada 4 | Who? Why? How? Searching for the Cause of MS | 5 PROGRAM OVERVIEW PROgrAM prESENTERS Welcome to the 2010 North American Education Program, Who? Why? How? — Searching for the Cause of MS. The National JEFFREY L. BENNEtt, MD MS Society began offering national education programs in 1988. Professor of Neurology and Ophthalmology University of Colorado — Denver School of Medicine The first national teleconference reached 700 participants in 60 DAvid A. HAFLER, MD sites. Since that time, we have utilized a range of technologies to Gilbert H. Glaser Professor of Neurology expand our audience throughout North America. Chairman, Department of Neurology Yale School of Medicine PAUL W. O’CONNOR, MD, MSC, FRCPC Director, University of Toronto Program in Multiple Sclerosis By archiving our programs on National Scientific and Clinical Advisor, MS Society of Canada the National MS Society web- Near the end of the year the site (nationalMSsociety.org), we program will also be available PAtriCIA A. O’LOONEY, PHD have made it possible for people on the National MS Society Vice President of BioMedical Research around the world to share the website as part of MS Learn National MS Society information as well. Online (nationalMSsociety.org/ MSLearnOnline) for anyone In an effort to reach the broad- who is unable to participate in BENJAmiN M. SEGAL, MD est possible audience, and a program or would like to view Holtom-Garrett Professor of Neurology maintain the flexibility of our or share the program more than Director, Multiple Sclerosis Center programming, we are again once. In the video program, res- University of Michigan providing this year’s program earchers discuss how understanding as a videotaped conference, the causes of MS can provide thus enabling the chapters of HELEN TREMLEtt, PHD hope for future MS treatments the National MS Society and and possibly a world free of MS. Assistant Professor, Department of Neurology the MS Society of Canada University of British Columbia the opportunity to offer the This program book provides an program to audiences at their in-depth look at the etiology, JErrY S. WOLINSKY, MD convenience over the course or the study of the causes, of of the year. multiple sclerosis. Bartels Family and Opal C. Rankin Professor of Neurology University of Texas Health Science Center at Houston 6 | Who? Why? How? Searching for the Cause of MS | 7 prESENTER BIOgrAphiES Dr. Jeffrey L. Bennett is cur- rently Professor of Neurology and Ophthalmology at the University of Colorado Denver and is a faculty member of the Dr. Bennett is internationally Rocky Mountain MS Center recognized as a leader in the JEFFREY L. at Anschutz Medical Campus. fields of neuroimmunology, Dr. Bennett maintains active BENNEtt, MD Dr. Bennett attended Case West- neuro-ophthalmology, and specialty practices in neuro- ern Reserve University, where demyelinating disease. He directs ophthalmology and multiple Professor of Neurology he graduated summa cum laude clinical and basic research sclerosis, and is regularly voted and Ophthalmology with degrees in Biochemistry programs on optic neuritis, one of the Best Doctors in University of Colorado — and Philosophy. He received multiple sclerosis, and neuro- America. In 2006, he received Denver School of Medicine his medical and doctoral degrees myelitis optica. His research the Stephen Reingold Award at Stanford University. Dr. Bennett is supported by the National from the National Multiple completed his internship and Institutes of Health, National Sclerosis Society. Dr. Bennett residency in Neurology at the Multiple Sclerosis Society, Guthy- has written many clinical and University of Colorado, fellow- Jackson Charitable Foundation, scientific publications, been ship in neuroophthalmology at and private industry. In the awarded