S1PR1 and secondary progressive multiple sclerosis: The S1PR-1,5 modulator siponimod, a second generation S1P agonist5, has shown significant effects in reducing the risk of 3-month confirmed disability progression and brain atrophy in secondary progressive multiple sclerosis (SPMS) patients compared to placebo in the EXPAND study6, and has been the first medication to be approved by the FDA as treatment for SPMS in 2019.