Multiple Sclerosis: Current Treatments and Future Promise

Joseph P. Van Der Meulen Symposium in Clinical Neuroscience Multiple Sclerosis: Current Treatments and Future Promise Saturday, May 12, 2012 Louis B. Mayer Auditorium USC Health Sciences Campus Los Angeles, California presented by Office of Continuing Medical Education and the Department of Neurology

JOSEPH P. VAN DER MEULEN, M.D. The annual Joseph P. Van Der Meulen Symposium in Clinical Neuroscience honors Dr. Van Der Meulen, former Chairman of the Department of Neurology at the University of Southern California, for his contributions to the development of clinical and basic neuroscience. Dr. Van Der Meulen continues at USC as Professor of Neurology and Vice President for Health Affairs, Emeritus. Dr. Van Der Meulen was born in Boston, Massachusetts and educated at the Public Latin School and Boston College before receiving his M.D. from Boston University. He completed an internal medicine internship at Bellevue Hospital (Cornell Service) in New York and received his neurology training at the Harvard Neurological Unit of the Boston City Hospital under Dr. Derek Denny-Brown. He subsequently spent two years at the Karolinska Institute studying neurophysiology with Professor Ragnar Granit, a Nobel Laureate. After serving on the faculty at Harvard and Case-Western Reserve, Dr. Van Der Meulen joined the Department of Neurology at USC in 1971, serving as Chairman until 1979. He served as Vice President for Health Affairs (1977-2005), and Director of the Independent Health Professions (1991-2005). During his tenure as Chairman of Neurology, he restructured the department and initiated the development of neuroscience. He served as Dean of the School of Medicine in 1985 and 1986 and as Interim Dean from 1995-1997. In addition to his organizational and administrative contributions, he has continued to teach and practice clinical neurology. His continuing activities on behalf of the medical community, the USC family, and the development of clinical and basic neurosciences make him a leader in education, health care, and research in the United States. NEEDS ASSESSMENT AND COURSE DESCRIPTION Multiple Sclerosis (MS) is a complex neurological disease that has been diagnosed in approximately 400,000 individuals in the United States, with worldwide estimates of 1.2 million, and rising. It is the most common cause of nontraumatic disability in young adults and is typically diagnosed between the ages of 20-40 although diagnoses at younger and older ages are not uncommon. Economic costs of this disease are estimated at $10 billion annually. Although the cause of MS is unknown, it is believed that an autoimmune attack on myelin in the central nervous system is triggered by environmental factors in genetically 1 susceptible individuals. Clinically, MS can take one of several forms, from a relatively mild relapsing-remitting form, to rapidly progressive disease. Symptoms, disease course, and treatment response are variable and at this point largely unpredictable, presenting challenges to recognition and management. Research in the area of biomarkers is beginning to shed light on some 2 3 of these areas. Multiple clinical trials have shown that early diagnosis and treatment of MS can delay disability. To this end, 4 the diagnostic criteria have been modified to incorporate MRI data which facilitate accurate diagnosis as early as possible. New insights into epidemiology, genetics, pathogenesis and treatment have been emerging at a rapid pace. New state-of-the art MRI techniques have facilitated earlier diagnosis and have contributed to a better understanding of inflammatory and 5 neurodegenerative characteristics of the disease. Genetic, epidemiologic and immunologic studies have provided new information about risk factors for developing MS, susceptibility to different forms of MS, and may also assist in predicting 6,7,8,9 response to currently approved disease modifying drugs. New research efforts have provided information about the role 10,11 of race and ethnicity in disease presentation and activity, and have revealed special characteristics of MS in children. MS is unique among many neurological diseases in that many disease modifying drugs are available that are capable of controlling inflammation and delaying neurodegenerative disease progression. Promising new disease modifying drugs are currently being 12 tested in clinical trials which have resulted in FDA applications, and several new strategies to promote neural repair and 13 regeneration are being explored, including those that use or target stem cells. Given the rapid pace of discovery and the changing armamentarium for treatment it is essential for neurologists and other caretakers to be well informed in order to translate these advances to best clinical practice. References 1 Courtney AM, et al. Multiple Sclerosis. Med Clin North Am. 2009;93(2):451-476. 2 Hecker M, Paap BK, Goertsches RH, Kandulski O, Fatum C, et al. (2011) Reassessment of Blood Gene Expression Markers for the Prognosis of Relapsing-Remitting Multiple Sclerosis. PLoS ONE 6(12): e29648. doi:10.1371/journal.pone.0029648. 3 e.g. Champions Study Group. Neurology. 2006;66:678-684. 4 Polman CH, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292-302. 5 Ali EN, Buckle GJ. Neuroimaging in multiple sclerosis. Neurol Clin. 2009;27(1):203-219. 6 International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476: 214-219. 7 Edwards L, et al. Central Inflammation versus peripheral regulation in Multiple Sclerosis. J Neurol. 2011; 258(8):1518-27. 8 Axtell R, Chander R, Steinman l. (2012) Clinic Rev Allerg Immunol DOI 10.1007/s12016-011-8296-5. 9 Freedman et al. Recognizing and treating suboptimally controlled multiple sclerosis: steps toward regaining command. Curr Med Res Opin. 2009;25(10):2459-2470. 10 Yeh EA, et al. Pediatric multiple sclerosis. Nat Rev Neurol. 2009;5(11):621-631. 11 Chitnis T, et al. Pediatric Multiple Sclerosis, Neurol Clin. 2011;29:481 505. 12 Stuve O, et al. Translational research in neurology and neuroscience 2010. Arch Neurol. 2010;67(11):1307-1315. 13 Uccelli A, et al. Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurology. 2011;10(7):649-656. This course will address current therapy after outlining essentials of pathophysiology and diagnosis. Management issues such as treatment choice and assessment of efficacy will be outlined. Promising future treatments for both prevention of new lesion and restoration of existing damaged tissue will be presented.

COURSE OBJECTIVES At the conclusion of this program, the participant should be able to: Implement the most current diagnostic criteria in order to facilitate early recognition of MS Explain current concepts in the pathophysiology and how this relates to treatment of MS Evaluate the complex genetics of MS and what they tell us about MS pathogenesis Cite and assess current and future treatment modalities, including risk profiles and mechanisms of action Evaluate the contributions of epidemiology and ethnicity in MS management Apply MRI data in the diagnosis and prognosis of the individual patient Assess treatment efficacy Define the status of neuroregenerative medicine in MS SCHEDULE 7:15 a.m. Registration and Continental Breakfast 8:00 a.m. Welcome and Introductory Remarks Margaret Burnett, MD and Leslie P. Weiner, MD 8:15 a.m. Multiple Sclerosis Overview / Pathophysiology Lawrence Steinman, MD 9:15 a.m. MRI in Diagnosis and Prognosis Nancy L. Sicotte, MD 10:15 a.m. Break 10:30 a.m. Epidemiology of Multiple Sclerosis Annette M. Langer-Gould, MD, PhD, MS 11:15 a.m. Ethnic Influences in Multiple Sclerosis Lilyana Amezcua, MD 12:00 noon Panel Discussion Drs. Amezcua, Langer-Gould, Sicotte, and Steinman 12:15 p.m. Lunch 2:15 p.m. Current Therapies for Multiple Sclerosis and Possible Algorithms for Their Use Regina Berkovich, MD, PhD 2:45 p.m. New and Emerging Therapies for Multiple Sclerosis Margaret Burnett, MD 3:15 p.m. Break 3:30 p.m. Pediatric Multiple Sclerosis: What It Tells Us about Multiple Sclerosis and How Management Differs From the Adult Patient Emmanuelle L. Waubant, MD, PhD 4:15 p.m. Neuroprotection, Neuroregeneration and Stem Cells Leslie P. Weiner, MD 5:00 p.m. Panel Discussion Drs. Berkovich, Burnett, Waubant, and Weiner 5:15 p.m. Adjourn 1:15 p.m. The Complex Genetics of Multiple Sclerosis Speaker to be determined Desirable Physician Attributes: In alignment with the CME mission of the Keck School of Medicine, programs are planned in the context of desirable physician attributes as designated by the ACGME/ABMS and the Institute of Medicine: 1) Patient Care and Patient Centered Care, 2) Medical Knowledge, 3) Practice-based Learning, 4) Interpersonal and Communication Skills, 5) Professionalism, 6) Systems-based Practice, 7) Work in Interdisciplinary Teams, 8) Apply Quality Improvement, 9) Utilize Informatics, and 10) Employ Evidence-based practice. This program and the objectives have been developed in the context of attributes 1, 2, 3, 5, and 10. CME CREDIT The Keck School of Medicine of the University of Southern California is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. The Keck School of Medicine of the University of Southern California designates this live activity for a maximum of 7.5 AMA PRA Category 1 Credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity. The California State Board of Registered Nursing accepts courses approved for AMA PRA Category 1 Credits as meeting the continuing education requirements for license renewal. ACKNOWLEDGMENT We gratefully acknowledge an educational grant in support of the program from Elan Pharmaceuticals, Inc.

COURSE FACULTY COURSE DIRECTOR Keck School of Medicine of USC Margaret Burnett, MD Assistant Professor of Neurology and Neuropathology Director, LAC+USC Multiple Sclerosis Clinic GUEST FACULTY Annette M. Langer-Gould, MD, PhD, MS Research Scientist, Neurology Department of Research and Evaluation Kaiser Permanente Southern California Associate Clinical Professor of Neurology Keck School of Medicine of USC Nancy L. Sicotte, MD Director, Multiple Sclerosis Program Department of Neurology Cedars-Sinai Medical Center Associate Professor of Neurology David Geffen School of Medicine at UCLA Los Angeles, California Lawrence Steinman, MD George A. Zimmerman Professor of Neurological Sciences, Neurology, Genetics and Pediatrics Stanford University School of Medicine Stanford, California Emmanuelle L. Waubant, MD, PhD Associate Professor of Neurology University of California, San Francisco, School of Medicine San Francisco, California FACULTY AT THE KECK SCHOOL OF MEDICINE University of Southern California Lilyana Amezcua, MD Assistant Professor of Neurology Division Co-chief, MS Comprehensive Care Center Regina Berkovich, MD, PhD Assistant Professor of Neurology Leslie P. Weiner, MD Professor of Neurology, Molecular Microbiology and Immunology Richard Angus Grant, Sr., Chair in Neurology Leslie P. Weiner Chair in Neurology FACULTY DISCLOSURE Current guidelines state that participants in continuing medical education activities should be aware of any affiliation or financial interest that could affect the speaker s presentation(s). The Accreditation Council for Continuing Medical Education policy mandates that the CME provider adequately manage identified potential conflicts of interest prior to the educational activity. Faculty members have completed disclosure forms and potential conflicts of interest have been reviewed and resolved. All disclosures will be listed in the course syllabus. Enjoy beautiful Los Angeles... Photo credits: Cover, Keck Medical Center - Jose Aparicio; Los Angeles Beach - Joe Schlabotnik; Disney Concert Hall - Alan Turkus; Downtown Los Angeles - Jose Aparicio. Used with permission.

COURSE INFORMATION Course Date: Saturday, May 12, 2012 Tuition: $50 if registered and paid by noon PST on 5/11/12; $65 if registering or paying on site. Tuition is non-refundable. Pre-registration closes at noon on Friday, May 11, 2012. Location: Louis B. Mayer Auditorium, Keith Administration Building, USC Health Sciences Campus, 1975 Zonal Avenue, Los Angeles, California 90033. Registration, Continental Breakfast and Exhibits: 7:15 a.m. to 8:00 a.m., Louis B. Mayer Auditorium Lobby Parking and lunch are provided. Parking instructions and a map to the Health Sciences Campus will be emailed to registrants before the course. Information: For additional information, call 323-442-2555 or 800-USC-1119. FAX application to 888-665-8650 (toll free). E-mail for CME course information: usccme@usc.edu Web site: www.usc.edu/cme To register on line, go to http://bit.ly/gsomxu Registration confirmation and parking information will be emailed. Please provide email address when registering! Special Needs: Advance notice of any special needs by May 1 will help us serve you better. COURSE APPLICATION Multiple Sclerosis: Current Treatment and Future Promise (#2705) May 12, 2012 Tuition: $50 if registered and paid by noon PST on 5/11/12; $65 if registering or paying on site. Please print: Name: (Last) (First) (Degree: MD, DO, RN, etc.) Medical License Number: Email*: Daytime phone: ( ) Fax: ( ) Mailing address: City: State: Zip + 4: Specialty: Please mark one: Check payable to USC enclosed I wish to pay by credit card VISA OR MASTERCARD ONLY Card Number: Expiration Date: Amount: $ Authorized signature: Please mail to Office of Continuing Medical Education, Keck School of Medicine of USC, 1975 Zonal Avenue, KAM 317, Los Angeles, CA 90033-1039. To make course reservations, call 323-442-2555 or 800-USC-1119. Registrations may be faxed to 888-665-8650 (toll free). To register on line, go to http://bit.ly/gsomxu Courses are subject to cancellation. Please check with the CME office for course availability if you register within three weeks of the starting date. USC will not refund travel costs for canceled courses. * Registration confirmation and parking information will be emailed. Please provide email address when registering!

Office of Continuing Medical Education Keck School of Medicine of USC University of Southern California 1975 Zonal Avenue, KAM 317 Los Angeles, California 90033-1039 Multiple Sclerosis: Current Treatment and Future Promise The Joseph P. Van Der Meulen Symposium in Clinical Neuroscience Saturday, May 12, 2012 Louis B. Mayer Auditorium, USC Health Sciences Campus Non-Profit Organization U.S. Postage PAID University of Southern California