title: A mechanistically novel, first oral therapy for multiple sclerosis: the development of fingolimod (FTY720, Gilenya).
abstract: 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.
authors.affiliation: Department of Molecular Biology and Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.forename: Volker
authors.initials: V
authors.lastname: Brinkmann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D055808:Drug Discovery; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D011409:Propylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000378:metabolism; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use
chemical_list: D007155:Immunologic Factors; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine