Multiple sclerosis

New therapies challenge the very definition of multiple sclerosis (MS). By classic definitions, MS is a chronic neurological disease characterized by plaques or scars in the central nervous system (CNS) as a result of demyelization and atrophy of neuronal axons. However, for most diagnosed with MS, symptoms and progression are much more heterogeneous than that definition would imply. For most with MS, the initial symptoms include a relapsing and remitting inflammatory phase (RR-MS), which responds to immunotherapy. Natural history studies of clinical relapse rates, a primary endpoint used in most phase III treatment trials, report incidence of relapses from 0.5 to 2 per year (Weinshenker and Ebers, 1987). With time, most RR-MS patients transition to what has been characterized as a non-inflammatory secondary progressive form of the disease (SP-MS). Immunotherapies that target the inflammatory phase of MS may not be effective once the transition occurs. In addition, a proportion of those diagnosed with MS exhibit a more aggressive form of MS that does not show significant remission cycles nor respond to the same therapies. This aggressive form of the disease was termed primary progressive (PP-MS) using consensus data from an international survey of clinicians for standard definitions of these common clinical MS courses (Lublin and Reingold, 1996).