Howard L. Weiner, M.D. ,Multiple Sclerosis Center Brigham & Women's Hospital Massachusetts General Hospital Harvard Medical School
Boston, Massachusetts

It is now assumed that multiple sclerosis is a cell mediated autoimmune disease directed against CNS myelin components. A large number of immune therapies have been shown to help MS although they may be only partially effective and effective at only certain stages of disease. It is also becoming increasing clear that early intervention is required for optimal effect of immune therapy in MS. Current ABC drugs are only partially effective although some patients are good responders. It appears that most drugs act by affecting the class of immune response either decreasing interferon gamma and IL-12 or increasing IL-10 and TGF-beta. Affecting cell migration to the nervous system may also be a mechanism. Because MS is a multi-factorial and heterogeneous disease, there will be responders and non-responders to each "effective" therapy. The earlier treatment is initiated, the more likely it is to be effective. Examples include cyclophosphamide, which is less effective the longer a patient is in progressive disease and interferons, which help earlier, when there is active lesion formation in the nervous system. Ultimately, the immunotherapy of MS will depend on identifying immune measures that link to the clinical course of MS and monitoring by MRI. It may be that most therapy ultimately is antigen specific even with "non-specific" therapy such as IFN-b, cyclophosphamide and mitoxantrone. When MS changes from the relapsing-remitting to the chronic progressive form, there not only is axonal damage in the nervous system, but the immune system itself becomes chronically activated. Finally, longer time frames must now be used to assess therapy in MS. Thus the ultimate goal is to both to treat early to prevent appearance of MS 5-10 years later and to administer therapy that will protect the patient from nervous system disability over a 20-30 year period. To achieve this, early therapy and combination therapy with multiple agents over time will be required.