Brain sphingosine-1-phosphate receptors: implication for FTY720 in the treatment of multiple sclerosis

Pharmacol Ther. 2008 Jan;117(1):77-93. doi: 10.1016/j.pharmthera.2007.08.005. Epub 2007 Sep 8.

Abstract

Multiple sclerosis (MS) is an autoimmune, neurological disability with unknown etiology. The current therapies available for MS work by an immunomodulatory action, preventing T-cell- and macrophage-mediated destruction of brain-resident oligodendrocytes and axonal loss. Recently, FTY720 (fingolimod) was shown to significantly reduce relapse rates in MS patients and is currently in Phase III clinical trials. This drug attenuates trafficking of harmful T cells entering the brain by regulating sphingosine-1-phosphate (S1P) receptors. Here, we outline the direct roles that S1P receptors play in the central nervous system (CNS) and discuss additional modalities by which FTY720 may provide direct neuroprotection in MS.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / physiopathology
  • Drug Delivery Systems
  • Fingolimod Hydrochloride
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / physiopathology
  • Propylene Glycols / pharmacology*
  • Propylene Glycols / therapeutic use
  • Receptors, Lysosphingolipid / drug effects
  • Receptors, Lysosphingolipid / metabolism*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Sphingosine / therapeutic use

Substances

  • Immunosuppressive Agents
  • Propylene Glycols
  • Receptors, Lysosphingolipid
  • Fingolimod Hydrochloride
  • Sphingosine