title: [Fingolimod therapy in multiple sclerosis--the issue of the pathomechanism].
abstract: Multiple sclerosis is an autoimmune inflammatory disease of the central nervous system with neurodegenerative chararacteristics. The newly discovered per os administrable drug fingolimod (FTY720) has a different mechanism of action than the current disease-modifying therapies. In vivo the drug binds to four out of the five sphingosine-1-phosphate receptors after phosphorylation. Fingolimod-phosphate (FTY720-P) causes internalization and degradation of the sphingosine-1-phosphate receptors in the membrane of lymphocytes thus in contrast to sphingosine-1-phosphate it acts like a functional antagonist. In experimental autoimmune encephalomyelitis--an animal model of multiple sclerosis--fingolimod blocks the sphingosine-1-phosphate gradient controlled lymphocyte egress from the lymph nodes and therefore reduces the peripheral lymphocyte count especially the encephalitogenic Th17 subset is reduced. Modulation of the sinus lining and blood-brain-barrier constructing endothelial cells also contributes to the complex mechanism of action. Additionally due to its liphohilic nature fingolimod is able to penetrate the blood brain barrier thus, beside its peripheral effects the drug can probably modulate the cells of the central nervous system directly. Presumably it can reduce neurodegeneration caused by astrogliosis through modification of astrocyte and oligodendrocyte activity. The results of current clinical studies show a bright perspective for both, the favourable therapeutic effects and the well-tolerated side effects.
authors.affiliation: Szent-Györgyi Albert Klinikai Központ, Neurológiai Klinika, Altalános Orvostudományi Kar, Szegedi Tudományegyetem és MTA-SZTA Idegtudományi Kutatócsoport, Szeged.
authors.forename: Lilla
authors.initials: L
authors.lastname: Tar
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008246:Lysophospholipids / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D010755:Organophosphates / Q000378:metabolism; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D058504:Th17 Cells / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: C525008:FTY 720P; D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D010755:Organophosphates; D011409:Propylene Glycols; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine