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Central nervous system-directed effects of FTY720 (fingolimod).
J Neurol Sci. 2008 Nov 15; 274(1-2):13-7.JN

Abstract

FTY720, also known as fingolimod, is an orally administered sphingosine-1-phosphate (S1P) analogue that is under investigation as a therapy for both relapsing-remitting (RR) and progressive forms of multiple sclerosis (MS). The demonstrated beneficial effect of FTY720 on disease activity in RR-MS patients and in the animal model experimental autoimmune encephalomyelitis (EAE) is largely attributed to effects on the systemic immune system. In addition, unlike other current systemic immuno-modulators used in MS, the lipophilic nature of FTY720 allows it to cross the blood-brain barrier (BBB). Since S1P receptors are expressed on all cell types, FTY720 has the potential to exert effects directly on the BBB and on resident cells of the CNS. The latter include cells implicated in regulating immune reactivity within the CNS (astrocytes, microglia), those that are targeted by the disease process (oligodendrocytes, neurons), and those involved in repair (oligodendrocyte progenitor cells). In vitro studies document the dose-dependent effects of FTY720 on neural cell survival, differentiation, and cytoskeletal dynamics. Animal model studies, specifically EAE, indicate an overall neuroprotective effect of FTY720 mediated at least in part by its actions within the CNS. Ongoing studies will need to define the direct and indirect (via immune-modulation) effects of FTY720 on the CNS across the broad clinical spectrum of MS.

Authors+Show Affiliations

Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4. veronique.miron@mcgill.caNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

18678377

Citation

Miron, Veronique E., et al. "Central Nervous System-directed Effects of FTY720 (fingolimod)." Journal of the Neurological Sciences, vol. 274, no. 1-2, 2008, pp. 13-7.
Miron VE, Schubart A, Antel JP. Central nervous system-directed effects of FTY720 (fingolimod). J Neurol Sci. 2008;274(1-2):13-7.
Miron, V. E., Schubart, A., & Antel, J. P. (2008). Central nervous system-directed effects of FTY720 (fingolimod). Journal of the Neurological Sciences, 274(1-2), 13-7. https://doi.org/10.1016/j.jns.2008.06.031
Miron VE, Schubart A, Antel JP. Central Nervous System-directed Effects of FTY720 (fingolimod). J Neurol Sci. 2008 Nov 15;274(1-2):13-7. PubMed PMID: 18678377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central nervous system-directed effects of FTY720 (fingolimod). AU - Miron,Veronique E, AU - Schubart,Anna, AU - Antel,Jack P, Y1 - 2008/08/03/ PY - 2008/04/10/received PY - 2008/06/27/accepted PY - 2008/8/6/pubmed PY - 2009/4/10/medline PY - 2008/8/6/entrez SP - 13 EP - 7 JF - Journal of the neurological sciences JO - J Neurol Sci VL - 274 IS - 1-2 N2 - FTY720, also known as fingolimod, is an orally administered sphingosine-1-phosphate (S1P) analogue that is under investigation as a therapy for both relapsing-remitting (RR) and progressive forms of multiple sclerosis (MS). The demonstrated beneficial effect of FTY720 on disease activity in RR-MS patients and in the animal model experimental autoimmune encephalomyelitis (EAE) is largely attributed to effects on the systemic immune system. In addition, unlike other current systemic immuno-modulators used in MS, the lipophilic nature of FTY720 allows it to cross the blood-brain barrier (BBB). Since S1P receptors are expressed on all cell types, FTY720 has the potential to exert effects directly on the BBB and on resident cells of the CNS. The latter include cells implicated in regulating immune reactivity within the CNS (astrocytes, microglia), those that are targeted by the disease process (oligodendrocytes, neurons), and those involved in repair (oligodendrocyte progenitor cells). In vitro studies document the dose-dependent effects of FTY720 on neural cell survival, differentiation, and cytoskeletal dynamics. Animal model studies, specifically EAE, indicate an overall neuroprotective effect of FTY720 mediated at least in part by its actions within the CNS. Ongoing studies will need to define the direct and indirect (via immune-modulation) effects of FTY720 on the CNS across the broad clinical spectrum of MS. SN - 0022-510X UR - https://www.unboundmedicine.com/medline/citation/18678377/Central_nervous_system_directed_effects_of_FTY720__fingolimod__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-510X(08)00320-1 DB - PRIME DP - Unbound Medicine ER -