Sphingosine-1-phosphate receptor modulators in multiple sclerosis

Abstract

The introduction of oral disease modifying therapies has transformed the treatment landscape for patients with multiple sclerosis (MS). Fingolimod (Gilenya®, Novartis, Basel, Switzerland), the first oral therapy to be approved, has demonstrated clinical efficacy as a result of modulation of subtype 1 sphingosine-1-phosphate (S1P1) receptors. This leads to retention of lymphocytes in the lymph nodes, preventing their entry into the central nervous system. However, fingolimod can cause adverse effects as a result of its interaction with other S1P receptor subtypes, which are expressed in numerous tissues, including cardiac myocytes. More selective S1P receptor agents are currently in phase II and III clinical development. Siponimod, ozanimod, ponesimod and amiselimod have demonstrated efficacy with improved safety profiles compared with fingolimod. While more long-term data are needed, these selective S1P receptor modulators appear to be promising options for the treatment of MS and other disorders associated with autoimmunity and inflammation.