The role dimethyl fumarate has on Remyelination in a Theiler's murine encephalomyelitis virus model of multiple sclerosis

There is a lack of, and a huge need for, therapy options that can stimulate remyelination in multiple sclerosis. Dimethyl fumarate (DMF) (Tecfidera™) is a promising treatment option which is administered orally. DMF is immunomodulatory and has been shown to have potential neuroprotection properties. The goal of this study was to examine whether treatment with DMF in a Theiler's murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) model of MS would stimulate remyelination. TMEV-IDD is a relatively accurate model of MS that exhibits demyelination, axonal loss, and a progressive disease course. To measure this remyelination, immunofluorescence microscopy was performed on spinal cord sections stained with either phosphorylated neurofilament [p-NF] (for axonal preservation), Nogo (newly formed myelin) or Olig2 (staining oligodendrocyte precursor cells-OPCs) in combination with Ki-67 (newly formed OPCs) and PDGF-R (differentiated OPCs). Cell expression was then quantified by a blinded observer. There was a highly significant increase in marker expression within the DMF treatment group, indicating effectivity of DMF in remyelination. Histologic evidence of significance in increased OPCs (P < 0.005), 40% reduction in demyelination and a highly a significant nearly five-fold increase in remyelination (P < 0.0001) were all found. It is indicated that the protective and antioxidative properties of DMF allow treatment with the medication to promote remyelination by preservation and differentiation of OPCs. This leads to axonal preservation within the TMEV-IDD model of MS. These results indicate the possibility for DMF to be a therapy causing remyelination within MS. Further studies would investigate the mechanisms involved as well as the improvement in clinical disability of virus affected models.