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[Fingolimod therapy in multiple sclerosis--the issue of the pathomechanism].
Ideggyogy Sz. 2012 Mar 30; 65(3-4):83-100.IS

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+Show Affiliations

Szent-Györgyi Albert Klinikai Központ, Neurológiai Klinika, Altalános Orvostudományi Kar, Szegedi Tudományegyetem és MTA-SZTA Idegtudományi Kutatócsoport, Szeged.No affiliation info available

Pub Type(s)

English Abstract
Journal Article
Review

Language

hun

PubMed ID

23136726

Citation

Tar, Lilla, and László Vécsei. "[Fingolimod Therapy in Multiple Sclerosis--the Issue of the Pathomechanism]." Ideggyogyaszati Szemle, vol. 65, no. 3-4, 2012, pp. 83-100.
Tar L, Vécsei L. [Fingolimod therapy in multiple sclerosis--the issue of the pathomechanism]. Ideggyogy Sz. 2012;65(3-4):83-100.
Tar, L., & Vécsei, L. (2012). [Fingolimod therapy in multiple sclerosis--the issue of the pathomechanism]. Ideggyogyaszati Szemle, 65(3-4), 83-100.
Tar L, Vécsei L. [Fingolimod Therapy in Multiple Sclerosis--the Issue of the Pathomechanism]. Ideggyogy Sz. 2012 Mar 30;65(3-4):83-100. PubMed PMID: 23136726.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Fingolimod therapy in multiple sclerosis--the issue of the pathomechanism]. AU - Tar,Lilla, AU - Vécsei,László, PY - 2012/11/10/entrez PY - 2012/11/10/pubmed PY - 2012/12/10/medline SP - 83 EP - 100 JF - Ideggyogyaszati szemle JO - Ideggyogy Sz VL - 65 IS - 3-4 N2 - 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. SN - 0019-1442 UR - https://www.unboundmedicine.com/medline/citation/23136726/[Fingolimod_therapy_in_multiple_sclerosis__the_issue_of_the_pathomechanism]_ L2 - http://www.diseaseinfosearch.org/result/4969 DB - PRIME DP - Unbound Medicine ER -