A mechanistically novel, first oral therapy for multiple sclerosis: the development of fingolimod (FTY720, Gilenya)

Discov Med. 2011 Sep;12(64):213-28.


Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Until recently, major therapeutic treatments have relied on agents requiring injection delivery. In September 2010, fingolimod/FTY720 (Gilenya, Novartis) was approved by the FDA as the first oral treatment for relapsing forms of MS. Fingolimod is a novel compound produced by chemical modification of a fungal precursor. Its active metabolite, formed by in vivo phosphorylation, modulates sphingosine 1-phosphate (S1P) receptors that are a subset of a larger family of cell-surface, G protein-coupled receptors (GPCRs) mediating the effects of bioactive lipids known as lysophospholipids. Fingolimod's mechanism of action in MS is not completely understood; however, its relevant biology indicates a fundamentally different mechanism compared to all previously approved MS therapies, with evolving research supporting both immunological and nervous system activities. This duality may herald a paradigm shift in the treatment of MS and other neurological disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Drug Discovery*
  • Fingolimod Hydrochloride
  • Humans
  • Immunologic Factors / therapeutic use
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Propylene Glycols / administration & dosage*
  • Propylene Glycols / chemistry
  • Propylene Glycols / immunology
  • Propylene Glycols / therapeutic use*
  • Receptors, Lysosphingolipid / antagonists & inhibitors
  • Receptors, Lysosphingolipid / metabolism
  • Sphingosine / administration & dosage
  • Sphingosine / analogs & derivatives*
  • Sphingosine / chemistry
  • Sphingosine / immunology
  • Sphingosine / therapeutic use


  • Immunologic Factors
  • Propylene Glycols
  • Receptors, Lysosphingolipid
  • Fingolimod Hydrochloride
  • Sphingosine