Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that affects millions of patients worldwide. The current disease-modifying therapies (DMTs) that are widely used to treat MS only show modest effects. Because MS is a chronic disease, it is important to develop treatments that have better long-term efficacy. Recently, several new-generation DMTs have been developed, most of which target specific immune molecules based on the assumption that MS is an autoimmune disease. These DMTs are designed to inhibit inflammation that is thought to directly cause demyelination. Preliminary studies suggest that these new therapies are likely to show a greater effect in reducing relapses in early MS patients, although their long-term efficacy is still unknown. In contrast, it was recently reported that the initial course of MS does not significantly influence long-term disability and that disability increases approximately at the same rate despite variable relapse frequencies. Furthermore, new neuropathological evidence now argues against the autoimmune hypothesis and suggests that MS is a primary oligodendrogliopathy disease in which the inflammatory response may be a mere epiphenomenon. So can we be optimistic about the unproven long-term outcomes of new DMTs or should we reconsider the pathogenesis of MS when developing more disease-specific treatments?