Does Siponimod Exert Direct Effects in the Central Nervous System?

Cells. 2020 Jul 24;9(8):1771. doi: 10.3390/cells9081771.

Abstract

The modulation of the sphingosine 1-phosphate receptor is an approved treatment for relapsing multiple sclerosis because of its anti-inflammatory effect of retaining lymphocytes in lymph nodes. Different sphingosine 1-phosphate receptor subtypes are expressed in the brain and spinal cord, and their pharmacological effects may improve disease development and neuropathology. Siponimod (BAF312) is a novel sphingosine 1-phosphate receptor modulator that has recently been approved for the treatment of active secondary progressive multiple sclerosis (MS). In this review article, we summarize recent evidence suggesting that the active role of siponimod in patients with progressive MS may be due to direct interaction with central nervous system cells. Additionally, we tried to summarize our current understanding of the function of siponimod and discuss the effects observed in the case of MS.

Keywords: astrocytes; demyelination; fingolimod; inflammation; microglia; multiple sclerosis; neuroprotection; siponimod; sphingosine-1 phosphate.

Publication types

  • Review

MeSH terms

  • Animals
  • Azetidines / metabolism*
  • Benzyl Compounds / metabolism*
  • Central Nervous System / physiopathology*
  • Disease Models, Animal
  • Humans
  • Mice
  • Multiple Sclerosis / drug therapy*
  • Sphingosine 1 Phosphate Receptor Modulators / metabolism*

Substances

  • Azetidines
  • Benzyl Compounds
  • Sphingosine 1 Phosphate Receptor Modulators
  • siponimod