Ozanimod is a selective sphingosine 1-phosphate receptor 1 and 5 modulator under development by Celgene, for the treatment of relapsing remitting multiple sclerosis.
Here, we report that S1P receptor 1 (S1PR1) is elevated in reactive astrocytes in an autoimmunity independent mouse model of MS and that selective S1PR1 modulation is sufficient to ameliorate the loss of oligodendrocytes and demyelination.
This provides a basis of immunomodulatory drugs targeting S1P1 receptor such as FTY720, an immunosuppressive drug approved in 2010 as the first oral treatment for relapsing-remitting multiple sclerosis.
Fingolimod (FTY720), a S1P receptor 1 (S1PR1) functional antagonist and FDA approved drug for relapsing-remitting multiple sclerosis, partially blunted Aβ42-induced pro-inflammatory cytokine generation, suggesting that Spns2 promotes microglia pro-inflammatory activation through S1P-signaling.