Multiple sclerosis (MS) is classified as an organ-specific autoimmune disease. Genome-wide association studies have linked HLA and immune system genes to the disease, leaving little doubt that immunological factors contribute to disease pathogenesis [1]. In the early stages of MS, scattered foci of inflammation occur in the central nervous system, the target of the inflammatory response. When these inflammatory foci involve motor, sensory, or visual pathways, clinical relapses occur. With resolution of inflammation, patients recover and enter a clinical remission. Relapses occur during the relapsing-remitting stage of MS (RRMS) at a variable rate, both across and within patients. Studies using MRI have revealed frequent new lesions, defined as gadolinium-enhancing lesions or as new T2-hyperintense lesions. The frequency of new lesions seen on MRI exceeds that of clinical relapses by approximately 10 to 1. For MS treatment, all currently approved disease-modifying drugs target inflammation and are generally indicated for reduction of relapse frequency. In MS patients, relapses become less frequent over the initial 10–20 years of the disease, and are replaced by slowly advancing neurological disability. This stage is referred to as secondary progressive MS (SPMS). Mechanisms underlying the transition from RRMS to SPMS are not entirely understood, but there appears to be a transition from a mostly inflammatory pathology to one that is neurodegenerative and no longer dependent on inflammation. Although neurodegeneration is presumed to underlie progressive neurological disability in SPMS, axonal transection occurs at sites of CNS inflammation [2] and causes neurodegeneration during the early disease stages. There are no approved disease-modifying drugs that directly target neurodegeneration in MS.
