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Neurological S1P signaling as an emerging mechanism of action of oral FTY720 (fingolimod) in multiple sclerosis

Academic Article
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Overview

authors

  • Lee, C. W.
  • Choi, J. W.
  • Chun, Jerold

publication date

  • October 2010

journal

  • Archives of Pharmacal Research  Journal

abstract

  • FTY720 (fingolimod, Novartis) is a promising investigational drug for relapsing forms of multiple sclerosis (MS), an autoimmune and neurodegenerative disorder of the central nervous system. It is currently under FDA review in the United States, and could represent the first approved oral treatment for MS. Extensive, ongoing clinical trials in Phase II/III have supported both the efficacy and safety of FTY720. FTY720 itself is not bioactive, but when phosphorylated (FTY720-P) by sphingosine kinase 2, it becomes active through modulation of 4 of the 5 known G protein-coupled sphingosine 1-phosphate (S1P) receptors. The mechanism of action (MOA) is thought to be immunological, where FTY720 alters lymphocyte trafficking via S1P1. However, MOA for FTY720 in MS may also involve a direct, neurological action within the central nervous system in view of documented S1P receptor-mediated signaling influences in the brain, and this review considers observations that support an emerging neurological MOA.

subject areas

  • Animals
  • Drugs, Investigational
  • Fingolimod Hydrochloride
  • Humans
  • Immunosuppressive Agents
  • Lysophospholipids
  • Multiple Sclerosis, Relapsing-Remitting
  • Neuroglia
  • Phosphorylation
  • Prodrugs
  • Propylene Glycols
  • Protein Isoforms
  • Receptors, Lysosphingolipid
  • Signal Transduction
  • Sphingosine
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Research

keywords

  • Central nervous system
  • FTY720
  • Fingolimod
  • Multiple sclerosis
  • Sphingosine 1-phosphate receptors
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Identity

International Standard Serial Number (ISSN)

  • 0253-6269

Digital Object Identifier (DOI)

  • 10.1007/s12272-010-1008-5

PubMed ID

  • 21052934
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Additional Document Info

start page

  • 1567

end page

  • 1574

volume

  • 33

issue

  • 10

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