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Biomarkers in Multiple Sclerosis - Workshop Summary


Biomarkers in Multiple Sclerosis - Workshop Summary

  1. TITLE, DATE(S), LOCATION OF WORKSHOP

    "Biomarkers in Multiple Sclerosis"
    April 14-16, 2004, Washington D.C.

  2. INTRODUCTION

    Multiple sclerosis (MS) is a complex disease with several mechanisms contributing sequentially or simultaneously to its pathophysiology. Biomarkers, accompanying and able to dissect these processes promise tremendous value for (1) diagnostics and stratification of subcategories for MS and of disease stages (2) prediction of disease course, (3) treatment selection and improved prognosis for treatment success, and (4) the evaluation of novel therapeutics. Though it is unlikely that one of these markers could function as a true surrogate, biomarkers can provide insight into the mechanism of action of a drug and could suffice for the pre-screening of prospective therapeutics. The study of biomarkers has been strongly endorsed by the NIH Autoimmune Disease Coordinating Committee and was proposed by a committee the Institute of Medicine assembled on behest of the National Multiple Sclerosis Society. The goal of this NINDS workshop on "Biomarkers in Multiple Sclerosis" was the characterization and evaluation of biomarkers with relevance to MS disease processes such as inflammation, demyelination, oxidative stress, axonal damage, and remyelination and of their usefulness to advance categories 1 to 4 listed above.

    Organized by Drs. Martin, Utz, Bielekova and Hohlfeld, an international group of 86 participants that included NIH staff, basic researchers, clinicians, and industry and FDA representatives explored the current state of biomarker research for MS, barriers to progress, possible solutions and priorities. The conclusions of the workshop are planned to appear in a special edition of the journal "Disease Markers".

  3. BACKGROUND

    Several pathophysiological processes such as inflammation, demyelination, axonal damage and repair mechanisms contribute in the complex disease manifestation of MS. These processes are not uniformly represented across patient populations and can selectively predominate in individual patients. The varying degrees of involvement contribute to the observed heterogeneity in phenotypic expression of the disease, its prognosis and the response to therapies. Successful therapeutic intervention is currently assumed to require a combination of different therapeutic strategies that would target individual dominant pathophysiological processes. Such process-specific therapies will require the use of biomarkers to aid in the identification of the dominant mechanisms, in the selection of appropriate patient populations, and in the initial screening for efficacious agents. The coordinated efforts and continuing discussions of Magnetic Resonance Imaging (MRI) over the last 15 years have helped to advance the field and have made MRI the most advanced biomarker candidate for MS. The NINDS workshop on "Biomarkers in Multiple Sclerosis" intended to initiate discussion on similar collaborative efforts for non-imaging biomarkers such as gene expression, and disease-correlated fluctuations of biological molecules including radicals, lipids, and peptides.

    The following were among the questions addressed at the workshop:What is the current state of biomarker research in MS? In which areas can biomarkers already be employed, e.g. does the available data allow the use of biomarkers for prognostic or treatment decisions? Are biomarkers from blood or cerebrospinal fluid useful to separate the different phenotypic aspects of MS and do they at least to some extent reflect the underlying disease process, e.g. contribution of immune factors versus vulnerability of the central nervous system to damage? Finally, how can we link biomarker research including genomics and proteomics with magnetic resonance imaging-, clinical-, genetic- and pathological studies in the future?

  4. DISCUSSION

    The workshop began with an introduction into MS disease pathogenesis (Dr. Hohlfeld) and a statement of the workshop goals (Dr. Martin). The presentations were followed by a discussion of biomarker versus surrogate endpoint (Dr. Atkinson) which defined the latter as a substitute for a clinically meaningful endpoint that would accurately predict the effect of a therapeutic intervention. Talks on the role of biomarkers in therapeutic development programs (Dr. Walton) and for MS specifically (Dr. Bielekova) introduced presentations on types of biomarkers for MS such as neuroimaging (Dr. Arnold), biomarkers indicative of peripheral activation (Drs. Ransohoff, Berger, Khoury), of blood brain barrier disruption (Dr. Waubant), and of lesion formation and repair (Drs. Giovannoni, Werner). Day 2 concluded with presentations on biomarker disease examples such as cancer and amyotrophic lateral sclerosis (Drs. Srivastava, Bowser) and technologies for biomarker discovery such as antigen and DNA microarrays, proteomics and SNP analysis (Drs. Steinman, Stephan, Kantor, Hafler). Day 3 was dedicated to debate in three break-out groups termed 1) Diagnosis (MS categorization and disease course prediction); 2) Treatment (Drug screening and treatment outcome prediction); and 3) Making it Happen (Sample types and collection methods / Storage / Data collection / Natural history studies versus clinical trials / Assay standardization and validation). The discussions led to the following conclusions and recommendations.

  5. RECOMMENDATIONS/CONCLUSIONS

    The approval of immunomodulatory therapies has made placebo-controlled trials ethically questionable. Trials of novel therapeutics are now conducted as add-on studies and are expected to show smaller treatment effects above and beyond the approved therapeutics. This in turn leads to a need for larger samples sizes (a problem for the limited MS patient population) and longer trial duration and ultimately cost inflation. Biomarkers are expected to gain increasing importance in the pre-screening and evaluation of drugs before costly phase III efficacy trials are undertaken. Currently, there is no biomarker that could serve this purpose, except for potentially the use of neuroimaging.

    Biomarkers that predict therapy responses or identify disease subtypes might be most in reach and would serve important purposes such as cost savings by avoiding treatment failures and increase of statistical power for clinical trials via improved patient stratification. Biomarkers that help with MS diagnostic or would predict disease progression might be harder to come by. It was felt that true surrogate markers that could replace clinical outcome measures as primary endpoints for clinical trials would not be available for years to come if ever.

    The groups saw a need for both hypothesis- and discovery-driven approaches to biomarker discovery. Some of the presented technologies and their potentials raised enthusiasm about discovery-driven approaches which by some were seen as less hampered by pre-conceived notions about disease pathology.

    Participants agreed that biomarker data would best be gathered in conjunction with a clinical trial. Biomarker studies require similar phenotype characterizations and logistics and have the same statistical requirements. It was suggested that EVERY treatment trial should include a biomarker component. Biomarker stand-alone studies could be undertaken, but would be uneconomical as they would require similar infrastructure and stringent requirements as in a clinical trial. Sample repositories and data banks are needed as are validations of assays and the resolution of intellectual property issues for biomarker data gathered in conjunction with industry-sponsored trials. The NIAID Immune Tolerance Network and the NCI Early Detection Research Network were discussed in this context. Finally, an appeal was made for funding agencies to provide mechanisms that would accommodate the requirements for biomarker proposals. This would mean a shortening of the review cycle to allow piggy-backing with a parent clinical trial such as achieved by NIH's RFA "Hyperaccelerated Award/Mechanism in Immunomodulation Trials". It would also mean special study sections with expertise and an appreciation of such studies..

  6. PARTICIPANTS

    Jack Antel, M.D.
    Professor
    McGill University
    Montreal Neurological Institute
    Department of Neurology
    3801 University Street, Room 111
    Montreal, Quebec H3A 2B4
    Canada
    Tel: 514-398-8550
    Fax: 514-398-7371
    Email: jack.antel@mcgill.ca

    Douglas L. Arnold, M.D.
    Professor
    McGill University
    Montreal Neurological Institute
    Department of Neurology
    3801 University Street, WB321
    Montreal, Quebec H3A 2B4
    Canada
    Tel: 514-398-8185
    Fax: 514-398-2975
    Email: doug@mrs.mni.mcgill.ca
    cc: ellie@mrs.mni.mcgill.ca

    Arthur J. Atkinson, Jr., M.D.
    Senior Advisor in Clinical Pharmacology
    National Institutes of Health
    Warren G. Magnuson Clinical Center
    10 Center Drive
    Building 10, Room 1C-227
    Bethesda, MD 20892-1165
    Tel: 301-435-8791
    Fax: 301-480-7307
    Email: aatkinson@cc.nih.gov

    Scott R. Barnum, Ph.D.
    Associate Professor
    University of Alabama at Birmingham
    Department of Microbiology
    845 19th Street South
    Bevill Biomedical Sciences Research Building, Room 842
    Birmingham, AL 35294
    Tel: 205-934-4972
    Fax: 205-934-4985
    Email: sbarnum@uab.edu

    Amit Bar-Or, M.D.
    Assistant Professor
    McGill University
    Montreal Neurological Institute
    Department of Neurology-Neurosurgery and Microbiology-Immunology
    3801 University Street, Room 111
    Montreal, Quebec, H3A2B4
    Canada
    Tel: 514-398-5132
    Fax: 514-398-7371
    Email: amit.bar-or@staff.mcgill.ca

    Karen Bateman
    Program Analyst
    National Institutes of Health
    National Institute of Neurological Disorders and Stroke
    6001 Executive Boulevard
    Neruoscience Center Building, Room 2121A
    Bethesda, MD 20892
    Tel: 301-496-1431
    Fax: 301-480-2424
    Email: kb287y@nih.gov

    Thomas Berger, M.D.
    Professor
    University of Innsbruck
    Department of Neurology
    Anichstrasse 35
    Innsbruck, A-6020, Austria
    Tel: +43-512-504-3860
    Fax: +43-512-504-4260
    Email: Thomas.berger@uibk.ac.at

    Christopher T. Bever. M.D.
    Professor of Neurology
    Director, VA MS Center of Excellence-East
    University of Maryland / Baltimore VAMC
    Department of Neurology
    22 South Greene Street, Room N4W4C
    Baltimore, MD 21201
    Tel: 410-605-7061
    Fax: 410-605-7937
    Email: Christopher.bever@med.va.gov

    Bibiana Bielekava
    National Institutes of Health
    National Institute of Neurological Disorders and Stroke
    10 Center Drive
    Building 10, Room 5B16
    Bethesda, MD 20892-1400
    Tel: (301) 496-1801
    Fax: (301) 402-0373
    Email: BielekoB@ninds.nih.gov

    Dennis Bourdette, M.D.
    Chairman
    Oregon Health and Science University
    Department of Neurology
    3181 Southwest Sam Jackson Park Road
    Portland, OR 94239
    Tel: 503-494-7321
    Fax: 503-494-7242
    Email: bourdett@ohsu.edu
    cc: hendryk@ohsu.edu

    Robert P. Bowser, Ph.D.
    Associate Professor
    University of Pittsburgh
    School of Medicine
    Department of Pathology
    200 Lothrop Street
    Biomedical Science Tower, Room S-420
    Pittsburgh, PA 15261
    Tel: 412-383-7819
    Fax: 412-648-1916
    Email: bowser@np.awing.upmc.edu
    cc: Bowserrp@upmc.edu

    Christopher Bredeson, M.D.
    Assistant Professor
    Medical College of Wisconsin
    International Bone Marrow Transplant Registry
    8701 Watertown Plank Road
    Milwaukee, WI 53226
    Tel: 414-456-8787
    Fax: 414-456-6530
    Email: bredeson@mcw.edu
    cc: sandee@mcw.edu

    Celia F. Brosnan, Ph.D.
    Professor
    Albert Einstein College of Medicine
    Department of Pathology and Neuroscience
    1300 Morris Park Avenue
    Bronx, NY 10464
    Tel: 718-430-2140
    Fax: 718-430-3259
    Email: brosnan@aecom.yu.edu

    Peter A. Calabresi, M.D.
    Johns Hopkins Hospital
    600 North Wolfe Street
    Department of Pathology, # 627
    Baltimore, MD 21287-6965
    Tel: 410-614-1522
    Fax: 410-502-6736
    Email: calabresi@jhmi.edu

    Timothy Coetzee, Ph.D.
    Director Research Training Programs
    National Multiple Sclerosis Society
    733 Third Avenue, 6th Floor
    New York, NY 10017
    Tel: (212) 476-0478
    Fax: (212) 986-7981
    Email: timothy.coetzee@nmss.org
    cc: paula.grant@nmss.org

    Martin Daumer, M.D.
    Deputy Scientific Director
    Sylvia Lawry Centre for Multiple Sclerosis Research
    1 Smaninger Str. 22 c/o 1MSE
    Munich, D-81675
    Germany
    Tel: +49-89-4140-4358
    Fax: +41-89-4140-6049
    Email: daumer@slcmsr.org
    cc: hamschild@clcmsr.org

    Tobias J. Derfuss, M.D.
    Max-Planck-Institute of Neurobiology
    Department of Neuroimmunology
    Am Klopferspitz 18
    D-82152 Martinsried
    Germany
    Tel: +49-89-8578-3581
    Fax: +49-89-8578-3519
    Email: tsderfus@neuro.mpg.de

    Suhayl Dhib-Jalbut, M.D.
    Professor and Chair
    University of Medicine and Dentistry of New Jersey
    Robert Wood Johnson Medical School
    Department of Neurology
    97 Paterson Street
    New Brunswick, NJ 08901-0019
    Tel: 732-235-7732
    Fax: 732-235-7041
    Email: jalbutsu@umdnj.edu
    cc: prescoem@umdnj.edu

    Thomas R. Esch, Ph.D.
    Program Officer
    National Institutes of Health
    National Institute of Allergy and Infectious Diseases
    Division of Allergy, Immunology and Transplantation
    6610 Rockledge Drive, Room 3022
    Bethesda, MD 20892
    Tel: 301-451-8851
    Fax: 301-480-1450
    Email: tesch@nih.gov

    Gordon S. Francis
    Vice President
    Serono, Inc.
    Department of Neurology
    One Technology Place
    Rockland, MA 02370
    Tel: 781-681-2192
    Fax: 781-681-2902
    Email: Gordon.francis@serono.com
    cc: Patricia.mattos@serono.com

    Joseph A. Frank, M.D.
    Chief of Experimental Neuroimaging Section
    National Institutes of Health
    Laboratory of Diagnostic Radiology Research
    9000 Rockville Pike
    Building 10, Room BIN256
    Bethesda, MD 20892
    Tel: 301-402-3586
    Fax: 301-402-3216
    Email: jafrank@helix.nih.gov
    cc: twilliams2@cc.nih.gov

    Mark Freedman, M.D.
    The Ottawa Hospital – General Campus
    Division of Neurology
    501 Smyth Road, Room 6350, Box 601
    Ottawa, Ontario, K1H 8L6
    Canada
    Tel: 613-737-8917
    Fax: 613-737-8857
    Email: mfreedman@ottawahospital.on.ca

    Paul A. Fronhna, M.D., Ph.D., Pharm.D.
    Medical Director of Biotherapeutics and Clinical Pharmacology Genentech
    1 DNA Way, MS84
    South San Francisco, CA 94080
    Tel: 650-225-5803
    Fax: 650-225-3117
    Email: pharmer@gene.com

    Gavin Giovannoni, Ph.D.
    Institute of Neurology
    University College London
    National Hospital for Neurology and Neruosurgery
    Department of Neuroinflamation
    Queen Square
    London WC1N 3BG
    United Kingdom
    Tel: +44-20-7837-3611
    Fax: +44-20-7837-8553
    Email: g.giovannoni@ion.ucl.ac.uk
    cc: joalsop@ion.ucl.ac.uk

    Elizabeth Gretz, Ph.D.
    National Institutes of Health
    National Institute of Arthritis and Musculoskeletal and Skin Diseases
    Immunology and Inflammation Program
    6701 Democracy Boulevard, Suite 800
    Bethesda, MD 20892
    Tel: 301-594-5032
    Fax: 301-480-4543
    Email: gretze@mail.nih.gov

    Linda Griffith, M.D., Ph.D.
    Medical Officer
    National Institutes of Health
    National Institute of Allergy and Infectious Diseases
    Division of Allergy, Immunology and Transplantation
    6610 Rockledge Drive
    Room 3025, MSC 6601
    Bethesda, MD 20892
    Tel: 301-496-7104
    Fax: 301-480-1450
    Email: lgriffith@niaid.nih.gov

    David A. Hafler, M.D.
    Breakston Professor of Neurology
    Harvard Medical School
    Department of Neurology
    77 Avenue Louis Pasteur
    Boston, MA 02115
    Tel: 617-525-5330
    Fax: 617-525-5333
    Email: dhafler@rics.bwh.harvard.edu
    cc: egoldings@rics.bwh.harvard.edu

    Bernhard Hemmer, M.D.
    Associate Professor
    Heinrich-Heine-Universität Düsseldorf
    Deparmtent of Neurology
    Moorenstraße 5
    40225 Düsseldorf, Germany
    Tel: +49-211-811-9296
    Fax: +49-211-811-8469
    Email: beruhard.hemmer@uni-duesseldorf.de

    Reinhard Hohlfeld, M.D.
    Professor
    Institut für Klinische Neuroimmunologie
    Klinikum der LMU München, Großhadern
    Marchioninistr. 15
    D-81377 München
    Germany
    Tel: +49-089-7095-4780
    Fax: +49-089-7095-4782
    Email: Reinhard.Hohlfeld@med.uni-muenchen.de

    Thomas P. Jacobs, Ph.D.
    Program Director
    National Institutes of Health
    National Institute of Neurological Disorders and Stroke
    Neural Environment
    6001 Executive Boulevard
    Rockville, MD 20892
    Tel: 301-496-1431
    Fax: 301-480-2424
    Email: tj12g@nih.gov

    Steven Jacobson
    National Institutes of Health
    National Institute of Neurological Disorders and Stroke
    10 Center Drive
    Building 10, Room 5B16
    Bethesda, MD 20892-1400
    Tel: (301) 496-1801
    Fax: (301) 402-0373
    Email: JacobsonS@ninds.nih.gov

    Aaron B. Kantor, Ph.D.
    Director
    SurroMed
    Department of Cell and Molecular Biology
    1430 O'Brien Drive
    Menlo Park, CA 94025
    Tel: 650-420-2302
    Fax: 650 420 2400
    Email: akantor@surromed.com

    Samia J. Khoury, M.D.
    Associate Professor
    Brigham and Women's Hospital
    Harvard Institutes of Medicine/Harvard Medical School
    Department of Neurology
    77 Avenue Louis Pasteur
    Boston, MA 02115
    Tel: 617-525-5370
    Fax: 617-525-5252
    Email: ckhoury@rics.bwh.harvard.edu

    Rivka Kreitman, Ph.D.
    Vice President, Innovative R & D
    Teva Neuroscience
    1090 Horsham Road
    North Wales, PA 19454
    Tel: 215-591-8645
    Fax: 215-591-8826
    Email: rivka.kreitman@tevaneuro.com
    cc: lori.messner@tevaneuro.com

    Story Landis, Ph.D.
    Director
    National Institutes of Health
    National Institute of Neurological Disorders and Stroke
    31 Center Drive
    Building 31, Room 8A52
    Bethesda, MD 20892
    Tel: (301) 496-9746
    Email: landiss@ninds.nih.gov

    Paul V. Lehmann, M.D., Ph.D.
    Professor
    Case Western Reserve University
    Department of Pathology
    20900 Euclid Avenue, BRB 923
    Cleveland, OH 44118
    Tel: 216-321-0480
    Fax: 216-368-1357
    Email: pvl2@po.cwru.edu
    cc: pvl@immunospot.com

    David Leppert, P.D. Dr. med.
    University Hospitals Basel
    Departments of Neurology and Research
    Petersgraben 4
    Basel, CH-4031
    Switzerland
    Tel: +011-41-61-265-4166
    Fax: +011-41-61-265-5638
    Email: david.leppert@unibas.ch
    cc: dleppert@uhbs.ch

    Michael C. Levin, M.D.
    Associate Professor
    University of Tennessee Memphis
    Department of Neurology
    855 Monroe Avenue
    Link Building, # 415
    Memphis, TN 38163
    Tel: 901-448-2243
    Fax: 901-448-7440
    Email: mlevin@utmem.edu

    Roland Liblau, M.D., Ph.D.
    Hospital de Rangueil
    Department of Immunology
    1 Avenue Jean-Poulhes
    TSA 50032
    31059 Toulouse Cedex 9
    France
    Tel: +33-561-323-432
    Fax: +33-561-323-424
    Email: rolandliblau@hotmail.com

    Fred D. Lublin, M.D.
    Director
    Mount Sinai School of Medicine
    Corinne Goldsmith Dickinson Center for Multiple Sclerosis
    Department of Neurology
    5 East 98th Street
    New York, NY 10029
    Tel: 212 241 6854
    Fax: 212 423 0440
    Email: fred.lublin@mssm.edu

    Silva Markovic-Plese, M.D.
    Associate Professor
    University of North Carolina at Chapel Hill
    School of Medicine
    Department of Neurology
    6109 Neuroscience Research Building
    Chapel Hill, NC 27599
    Tel: 919-966-3701
    Fax: 919-843-4576
    Email: markovics@glial.med.unc.edu

    Roland Martin, M.D.
    National Institutes of Health
    National Institute of Neurological Disorders and Stroke
    10 Center Drive
    Building 10, Room 5B16
    Bethesda, MD 20892-1400
    Tel: (301) 496-1801
    Lab: (301) 402-4488
    Fax: (301) 402-0373
    Email: martinr@ninds.nih.gov

    Henry McFarland
    National Institutes of Health
    National Institute of Neurological Disorders and Stroke
    10 Center Drive
    Building 10, Room 5B16
    Bethesda, MD 20892-1400
    Tel: (301) 496-1801
    Fax: (301) 402-0373
    Email: mcfarlandh@ninds.nih.gov

    Edgar Meinl, M.D.
    Professor
    Max-Planck-Institute of Neurobiology
    Department of Neuroimmunology
    Am Klopferspitz 18,
    D-82152 Martinsried
    Germany
    Tel: +49-89-8578-3519
    Fax: +49-89-8995-0163
    Email: Meinl@neuro.mpg.de

    Paolo A. Muraro, M.D., Ph.D.
    Research Fellow
    National Institutes of Health
    National Institute of Neurological Disorders and Stroke
    Neuroimmunology Branch
    10 Center Drive, MSC 1400
    Building 10, Room 5B16
    Bethesda, MD 20892
    Tel: 301-594-7217
    Fax: 301-402-0373
    Email: murarop@ninds.nih.gov

    Richard A. Nash, M.D.
    Associate Professor/Associate Member
    University of Washington
    Fred Hutchinson Cancer Research Center
    Transplantation Biology Department
    Clinical Research Division
    1100 Fairview Avenue North
    PO Box 19024
    Seattle, WA 98109-1024
    Tel: 206-667-4978
    Fax: 206-667-6124
    Email: rnash@fhcrc.org

    John H. Noseworthy, M.D.
    Chair
    Mayo Clinic Rochester
    College of Medicine
    Department of Neurology
    200 First Street Southwest
    Rochester, MN 55905
    Tel: 507-284-2675
    Fax: 507-226-0178
    Email: noseworthy.john@mayo.edu

    Tomas Olsson, M.D., Ph.D.
    Professor
    Neuro & Immunology Unit
    Department of Clinical Neurosciences
    Karolinska Hospital
    CMM L8:04
    17176, Stockholm
    Sweden
    Phone:+46-8-5177-6242
    Fax: +46-8-5177-6248
    Email: Tomas.Olsson@cmm.ki.sc

    Patricia A. O'Looney, Ph.D.
    Director of Biomedical Research Programs
    National Multiple Sclerosis Society
    Research Programs Department
    733 Third Avenue, 6th Floor
    New York, NY 10017
    Tel: 212-476-0413
    Fax: 212-986-7981
    Email: patricia.olooney@nmss.org

    Gilmore O'Neill, M.B., M.Med.Sc.
    Associate Director
    Biogen IDEC
    Clinical Development Neurology
    14 Cambridge Center
    Cambridge, MA 02142
    Tel: 617-914-4725
    Fax: 617-679-3518

    Harry Openshew, M.D.
    Medical Officer
    National Institutes of Health
    National Institute of Allergy and Infectious Diseases
    Division of Allergy, Immunology and Transplantation
    6610 Rockledge Drive
    Room 3025, MSC 6601
    Bethesda, MD 20892
    Tel: 301-496-7104
    Fax: 301-480-1450

    Kirti R. Patel, Ph.D., M.D.
    Senior Scientist
    Aventis Pharmaceuticals CNS, Target Validation MS Team
    5203A, 1041 Route 202-206
    Bridgewater , NJ 08844
    Tel: 908-231-2631
    Email: kirti.patel@aventis.com

    Steven Pavletic, M.D.
    Head, Graft-Versus-Host and Autoimmunity Unit
    National Institutes of Health
    National Cancer Institute
    Experimental Transplantation and Immunology Branch
    9000 Rockville Pike
    Bethesda, MD 20892-1907
    Tel: 301-402-4899
    Fax: 301-435-2044
    Email: pavletis@mail.nih.gov

    Audrey S. Penn, M.D.
    Deputy Director
    National Institutes of Health
    National Institute of Neurological Disorders and Stroke
    31 Center Drive , MSC 2540
    Building 31 , Room 8A52
    Bethesda , MD 20892-2540
    Tel: 301-496-3167
    Fax: 301-496-0296
    Email: ap101d@nih.gov

    A. John Petkau, Ph.D.
    Professor
    University of British Columbia
    Department of Statistics
    333-6356 Agricultural Road
    Vancouver, British Columbia
    V6T 1Z2
    Canada
    Tel: 604-822-4673
    Fax: 604-822-6960
    Email: john@stat.ubc.ca

    Michael K. Racke, M.D.
    Professor
    University of Texas Southwestern Medical Center
    Department of Neurology and the Center for Immunology
    5323 Harry Hines Boulevard
    Dallas, TX 75390-9036
    Tel: 214-648-2330
    Fax: 214-648-9129
    Email: Michael.racke@utsouthwestern.edu

    Richard M. Ransohoff, M.D.
    Staff Neurologist
    Cleveland Clinic Foundation
    Lerner College of Medicine
    Department of Neuroscience
    9500 Euclid Avenue
    Cleveland, OH 44195
    Tel: 216-444-0627
    Fax: 216-444-7927
    Email: ransohr@ccf.org

    Stephen C. Reingold, Ph.D.
    Vice President
    National Multiple Sclerosis Society
    Research Programs Department
    733 Third Avenue
    New York, NY 10017-3288
    Tel: 212-476-0411
    Fax: 212-986-7981
    Email: stephen.reingold@nmss.org

    John R. Richert, M.D.
    Professor and Chair
    Georgetown University Medical Center
    Department of Microbiology and Immunology
    3900 Reservoir Road, NW
    Washington, DC 20057
    Tel: 202-687-1513
    Fax: 202-687-1800
    Email: richertj@georgetown.edu

    John W. Rose, M.D.
    Professor
    VA Medical Center
    Neurology Office
    500 Foothill Boulevard
    Salt Lake City, UT 84148
    Tel: 801-584-1292
    Fax: 801-582-6908
    Email: jrose@howard.genetics.utah.edu

    Noel R. Rose, M.D., Ph.D.
    Professor of Pathology
    Professor of Molecular Microbiology and Immunology
    Director, Johns Hopkins Center for Autoimmune Disease Research
    Bloomberg School of Public Health
    MMI-E5014
    615 N. Wolfe Street
    Baltimore, MD 21205
    Tel: 410-955-0330
    Fax: 410-955-0105
    Email: nrrose@jhmi.edu

    Richard A. Rudick, M.D.
    Director, Mellen Center
    Cleveland Clinic Foundation
    Department of Neurology
    9500 Euclid Avenue, U-10
    Cleveland, OH 44195
    Tel: 216-444-8603
    Fax: 216-445-7013
    Email: rudickr@ccf.org
    cc: lansok@ccf.org

    Edgar F. Salazar-Grueso, M.D.
    Vice President
    Head Corporate Clinical Development CNS/CV
    Berlex Pharmaceuticals
    PO Box 1000
    Montville, NJ 07045-1000
    Tel: 993-487-2760
    Fax: 707-988-8574
    Email: edger_salazar-grueso@berlex.com
    cc: susan_windecker@berlex.com

    Rupert Sandbrink, M.D., Ph.D.
    Department Head
    Schering AG
    Clinical Development CNS
    Sellerstrasse 31
    D-13442 Berlin
    Germany
    Tel: +49-30-468-17292
    Fax: +49-30-468-18243
    Email: Rupert.sandbrink@schering.de
    cc: birgit.grund@schering.de

    Benjamin M. Segal, M.D.
    Assistant Professor
    University of Rochester
    School of Medicine
    Department of Neurology
    Neuroimmunology Unit
    Rochester Multiple Sclerosis Center
    601 Elmwood Avenue, Box 605
    Rochester, NY 14642
    Tel: 585-273-3963
    Fax: 585-275-9953
    Email:Benjamin_segal@urmc.rochester.edu

    Krzysztof W. Selmaj, M.D., Ph.D.
    Professor of Medicine
    Łódź Medical University
    Department of Neurology
    ul. Kopcińskiego 22
    90-153 Łódź
    Poland
    Tel: +48-42-6776678
    Fax: +48-42-678-2293
    Email: kselmaj@afazja.am.lodz.pl

    Christopher A. Shaw, Ph.D.
    Associate Professor
    University of British Columbia
    Department of Medicine/Ophthalmology
    828 West 102 Avenue, Research Pavilion
    Vancouver, British Columbia V57128
    Canada
    Tel: 604-875-4111
    Fax: 604-875-4376
    Email: csshawlab@hotmail.com

    Per Soelberg Sorensen, M.D.
    Professor
    RigsHospitalet
    Department of Neurology – 2082
    9, Blegdamsvej
    2100 Copenhagen
    Denmark
    Tel: +45-3545-2080
    Fax: +45-3545-2626
    Email: pss@rh.dk
    cc: albert@rh.dk

    Sudhir Srivastava, Ph.D., M.P.H.
    National Institutes of Health
    National Cancer Institute
    Cancer Biomarkers Research Group
    6130 Executive Boulevard, Room 3147
    Rockville, MD 20852
    Tel: 301-435-1594
    Fax: 301-402-8990
    Email: srivasts@mail.nih.gov

    Lawrence Steinman, M.D.
    Professor of Neurology
    Chair of Interdepartmental Program in Immunology
    Stanford University
    Department of Neurology and Neurological Sciences
    Beckman B002
    Stanford, CA 94305
    Tel: 415-601-3778
    Fax: 650-725-0627
    Email: Steinman@stanford.edu

    Dietrich A. Stephan, Ph.D.
    Director TGen, The Translational Genomics Research Institute
    Neurogenomics Division
    400 North Fifth Street, Suite 1600
    Phoenix, AZ 85004
    Tel: 602-343-8727
    Fax: 602-343-8740
    Email: dstephan@tgen.org
    cc: jlemna@tgen.org

    Paul J. Utz, M.D.
    Assistant Professor
    Stanford University
    Department of Medicine/Immunology and Rheumatology
    269 Campus Drive, CCSR 2215A
    Stanford, CA 94305
    Tel: 650-724-5421
    Fax: 650-723-7509
    Email: pjutz@stanford.edu
    cc: sdickow@standord.edu

    Ursula Utz, Ph.D.
    National Institute of Neurological Disorders and Stroke National Institutes of Health
    6001 Executive Boulevard Neuroscience Center Building , Room 2134
    Bethesda, MD 20892
    Tel: 301-496-1431
    Fax: 301-480-2424
    Email: utzu@ninds.nih.gov

    Timothy L. Vollmer, M.D.
    Chair
    Barrow Neurological Institute
    Division of Neurology
    350 West Thomas Road, 8BN1
    Phoenix, AZ 85013
    Tel: 602-406-3390
    Fax: 602-406-7161
    Email: tvollmer@chw.edu
    cc: sconaway@chw.edu

    Rhonda R. Voskuhl, M.D.
    Professor
    University of California, Los Angles
    Department of Neurology
    Multiple Sclerosis Research and Treatment Program
    A-145 Reed Neurological Research Center
    710 Westwood Plaza
    Los Angeles, CA 90095
    Tel: 310-206-4636
    Fax: 310-206-9801
    Email: rvoskuhl@ucla.edu

    Marc K. Walton
    Supervisory Medical Officer
    CBER
    Food and Drug Administration
    WOC 2, Room 3047
    Rockville, MD 20852
    Tel: 301-827-5096
    Email: waltonm@cber.fda.gov

    Klaus-Peter Wandinger, M.D.
    Charite-University Medicine
    Institute of Neuroimmunology
    Klinische Neuroimmunologie
    Schumannstr 20/21
    10117 Berlin
    Germany
    Tel: +49-30-450-539-028
    Fax: +49-30-450-539-906
    Email: Klaus-peter.wandinger@charite.de
    cc: Andrew.mason@charite.de

    Emmanuelle L. Waubant, M.D., Ph.D.
    Assistant Professor
    University of California, San Francisco
    Multiple Sclerosis Center
    350 Parnassus Street, Suite 908
    San Francisco, CA 941173
    Tel: 415-514-2468
    Fax: 415-514-2443
    Email: Waubant@itsa.ucsf.edu

    Josiah Wedgwood, M.D., Ph.D.
    Chief, Immunodeficiency and Immunopathology Section
    Division of Allergy, Immunology and Transplantation
    6610 Rockledge Drive, Room 3019
    Bethesda, Md 20892
    Tel: 301-435-4418
    Fax: 301-480-1450
    Email: jwedgwood@niaid.nih.gov

    Howard L. Weiner, M.D.
    Robert L. Kroc Professor of Neurology
    Brigham and Women's Hospital
    Harvard Institutes of Medicine/Harvard Medical School
    Department of Neurology
    77 Avenue Louis Pasteur, Room 730
    Boston, MA 02115
    Tel: 617-525-5300
    Fax: 617-525-5252
    Email: hweiner@rics.bwh.harvard.edu
    cc: mstatham@rics.bwh.harvard.edu

    Brian G. Weinshenker, M.D.
    Professor
    Mayo Clinic at Rochester
    Department of Neurology
    200 First Street Southwest
    Rochester, MN 55905
    Tel: 507-538-1039
    Fax: 507-266-4419
    Email: weinb@mayo.edu
    cc: abbott.denise@mayo.edu

    Peter Werner, Ph.D.
    Associate Professor
    Albert Einstein College of Medicine
    Department of Neurology and Pathology (Neuropathology)
    F-117, 1300 Morris Park Avenue
    Bronx, NY 10461
    Tel: 718-430-3061
    Fax: 718-430-8785
    Email: pwerner@aecom.yu.edu
    cc: peterwerner@yahoo.com

    Jerry S. Wolinsky, M.D.
    Professor
    Department of Neurology
    University of Texas
    Health Science Center, Houston
    6431 Fannin Street
    Houston, TX 77030
    Tel: 713-500-7048
    Fax: 713-500-7041
    Email: jswolinsky@aol.com

    Takashi Yamamura, M.D., Ph.D.
    Director
    National Institute of Neuroscience, NCNP
    Department of Immunology
    4-1-1 Ogawahigashi, Kodaira,
    Tokyo 187-8502
    Japan
    Tel: +81-42-348-1723
    Fax: +81-42-346-1753
    Email: yamamura@ncnp.go.jp

    V. Wee Yong, Ph.D.
    Professor
    University of Calgary
    Department of Oncology and Clinical Neurosciences
    3330 Hospital Drive Northwest
    Calgary, Alberta T2N 4N1
    Canada
    Tel: 403-220-3544
    Fax: 403-283-8731
    Email: vyong@ucalgary.ca

    Frauke Zipp, Professor
    Charite-University Medicine
    Institute of Neuroimmunology
    Klinische Neuroimmunologie
    Schumannstr 20/21
    10117 Berlin
    Germany
    Tel: +49-30-450-539-028
    Fax: +49-30-450-539-906
    Email: frauke.zipp@charite.de
    cc: Andrew.mason@charite.de

Last updated March 19, 2009