N-acetylglucosamine analogs for the treatment of Multiple Sclerosis.

Abstract Multiple sclerosis (MS) is a T-cell mediated autoimmune disorder of the central nervous system. Current treatment strategies for MS are predominated by injectable therapies that do not target an underlying cause of the disease, have modest efficacy and have high cost and/or side effects that limit tolerability and compliance. An oral therapy that promotes self-tolerance by targeting an underlying disease mechanism, rather than broad and nonspecific immunosuppression, remains a major unmet need forthe management of MS. As a complex trait disease, multiple genetic and environmental factors combine to influence disease risk in MS. Our published data in both mice and humans indicates that multiple genetic and environmental risk factors for MS convergeto dysregulate protein N-glycosylation, thereby driving pathogenic autoimmune T cell responses. Therapeutic supplementation to N-glycan biosynthesis may provide the first therapy directly targeting an underlying cause of the disease. Indeed, supplementin