Dimethyl fumarate (DMF) is an oral agent for relapsing-remitting multiple sclerosis (RRMS). In this study, we investigated the therapeutic mechanism of DMF using experimental autoimmune encephalomyelitis (EAE). DMF treatment decreased the proliferation of T cells and the production of IL-17A and GM-CSF. DMF treatment also decreased the infiltration of macrophages into the central nervous system (CNS), and reduced the ratio of M1 vs M2 macrophages. Furthermore, DMF-treatment suppressed the deposition of complement C3 (C3) and development of reactive A1 astrocytes. The decrease in M1 macrophages, reactive A1 astrocytes, and C3 deposition in the CNS resulted in reduction of demyelination and axonal loss. This study suggests that the beneficial effect of DMF involves the suppression of M1 macrophages, reactive A1 astrocytes, and deposition of C3 in the CNS. 

Kouichi Ito and Suhayl Dhib-Jalbut received grant support from Teva Pharmaceuticals and Biogen Idec.