We have previously reported that SYN enters the central nervous system (CNS), suppresses inflammatory responses, and reduces microglial activation in in vitro and in vivo studies. DMS administration achieves higher receptor affinity and longer lasting concentrations in the CNS compared to SYN. This study compares the relative efficacy of SYN and DMS in suppressing EAE.

EAE was induced in SJL/J mice by immunization with proteolipid protein (PLP) 139-151 peptide. Treatment was performed daily via intraperitoneal (IP) injections from Days 10-28 post-immunization with either SYN 5 mg/kg, DMS 1 mg/kg, Vehicle, or Saline. Brain and spinal cord were harvested for H & E and multiplex immunofluorescence staining. Plasma and brain samples were obtained at for analyte concentration analysis.

Both SYN and DMS significantly reduced mean clinical disease score with DMS treatment (1.28) lower than SYN (1.78). SYN was lower than vehicle (2.01), but only DMS treatment was significantly lower (p=0.0031 **) than vehicle treatment. However, both SYN and DMS (p<0.0001 ****) had significantly lower scores than saline (2.91) treatment. Furthermore, DMS-treated mice had reduced meningeal, perivascular, and parenchymal infiltration of CD3+, CD4+ T cell infiltration at end of treatment (Day 28), with marked suppression of activated microglia/macrophage expression in the spinal cord.

Our results demonstrate that both the natural metabolite of DHA, SYN and DMS reduce  EAE severity in mice. However, DMS, has significantly greater efficacy than SYN in reducing EAE severity in this mouse model. Because DMS reduces both systemically derived lymphocytic infiltration and suppresses microglial/macrophage activation within the CNS, this agent has potential therapeutic value in treating both relapsing and progressive forms of multiple sclerosis (MS).