*3.2. Siponimod*

As previously indicated, SPM is a selective S1P1R and S1P5R modulator that readily crosses the BBB [78]. Preclinical studies indicate that it may preserve neurons by preventing excitotoxic synaptic degeneration [83], enhancing cell survival pathways [80,82], and promoting remyelination in the CNS [83]. Given the results of these preclinical studies, and because of the need to develop DMTs that might slow disability worsening in patients with secondary progressive multiple sclerosis (SPMS), it was decided to evaluate SPM efficacy in this patient population.
