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Neuroprotective Effect of Vesatolimod in an Experimental Autoimmune Encephalomyelitis Mice Model

Jiang, X;Song, Y;Fang, J;Yang, X;Mu, S;Zhang, J;

Multiple sclerosis (MS) is a chronic, demyelinating autoimmune disease accompanied by inflammation and loss of axons and neurons. Vesatolimod (VES, GS-9620) is a safe and well-tolerated agonist of toll-like receptor 7 with antiviral properties. To further develop possible therapeutic uses of VES, we assessed the effect of VES on MS using an Experimental autoimmune encephalomyelitis (EAE) mouse model which was induced in mice by MOG35-55 injection. Mice were monitored for clinical symptoms daily, and the treatment group was given VES at the onset of illness. The therapeutic effect of VES on EAE inflammation, demyelination, macrophage and T cells infiltration, and microglia activation was evaluated. Autophagy within the spinal cords of EAE mice was also preliminarily assessed. Treatment with VES significantly alleviated clinical symptoms of EAE from day 18 post-immunization and decreased the expression levels of inflammatory cytokines, particularly IL-12 (P40) and Eotaxin, in peripheral blood. It also inhibited demyelination in spinal cords, observed by immunofluorescent staining. Moreover, VES treatment reduced infiltration of CD3?+?T cells and CD107b?+?macrophages, activation of microglia, as well as inhibited the expression of autophagy-related proteins (ATG5, ATG7 and ATG12) in the spinal cords of EAE mice. Our results suggest that VES exhibits protective effects on EAE mice and has the potential to be a novel drug for the treatment of MS.