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[Basic mechanisms of action of fingolimod in relation to multiple sclerosis].
Rev Neurol. 2012 Jul 01; 55(1):31-7.RN

Abstract

INTRODUCTION

Fingolimod has recently been approved for the therapy of relapsing multiple sclerosis. This drug binds to different sphingosine-1-phosphate receptors.

AIM

To analyze basic mechanisms of action that can account for the efficacy of this drug in multiple sclerosis.

DEVELOPMENT

Fingolimod acts as an inverse agonist on sphingosine-1-phosphate receptors, inducing degradation of receptors. On lymphoid circulation, this effect causes retention in lymph nodes of naive and central memory T cells, including Th17 T lymphocytes, bearing CCR7 and CD62L receptors. As a result, the level of circulating T cells is markedly decreased. B ell circulation is impaired and complex effects on other immune cells are also induced. Fingolimod enters the central nervous system and binds to receptors on glial cells and neurons. In experimental autoimmune encephalomyelitis, the therapeutic efficacy of fingolimod is not only associated with a reduced entry of inflammatory cells into the nervous system, but also with a direct effect mostly on astroglial cells.

CONCLUSIONS

In multiple sclerosis patients, the available evidence indicates that fingolimod efficacy is directly associated with impairment of circulation of several T cell subsets and possibly B cells. Animal studies raise the possibility that an additional effect on glial cells might also contribute to the clinical efficacy.

Authors+Show Affiliations

Unidad y Laboratorio de Neuroinmunología, Servicio de Neurología, Hospital Universitario Puerta de Hierro-Majadahonda, 28035 Majadahonda, Espana. jgarciam.hpth@salud.madrid.orgNo affiliation info available

Pub Type(s)

English Abstract
Journal Article

Language

spa

PubMed ID

22718407

Citation

García-Merino, J Antonio, and Antonio J. Sánchez. "[Basic Mechanisms of Action of Fingolimod in Relation to Multiple Sclerosis]." Revista De Neurologia, vol. 55, no. 1, 2012, pp. 31-7.
García-Merino JA, Sánchez AJ. [Basic mechanisms of action of fingolimod in relation to multiple sclerosis]. Rev Neurol. 2012;55(1):31-7.
García-Merino, J. A., & Sánchez, A. J. (2012). [Basic mechanisms of action of fingolimod in relation to multiple sclerosis]. Revista De Neurologia, 55(1), 31-7.
García-Merino JA, Sánchez AJ. [Basic Mechanisms of Action of Fingolimod in Relation to Multiple Sclerosis]. Rev Neurol. 2012 Jul 1;55(1):31-7. PubMed PMID: 22718407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Basic mechanisms of action of fingolimod in relation to multiple sclerosis]. AU - García-Merino,J Antonio, AU - Sánchez,Antonio J, PY - 2012/6/22/entrez PY - 2012/6/22/pubmed PY - 2012/12/10/medline SP - 31 EP - 7 JF - Revista de neurologia JO - Rev Neurol VL - 55 IS - 1 N2 - INTRODUCTION: Fingolimod has recently been approved for the therapy of relapsing multiple sclerosis. This drug binds to different sphingosine-1-phosphate receptors. AIM: To analyze basic mechanisms of action that can account for the efficacy of this drug in multiple sclerosis. DEVELOPMENT: Fingolimod acts as an inverse agonist on sphingosine-1-phosphate receptors, inducing degradation of receptors. On lymphoid circulation, this effect causes retention in lymph nodes of naive and central memory T cells, including Th17 T lymphocytes, bearing CCR7 and CD62L receptors. As a result, the level of circulating T cells is markedly decreased. B ell circulation is impaired and complex effects on other immune cells are also induced. Fingolimod enters the central nervous system and binds to receptors on glial cells and neurons. In experimental autoimmune encephalomyelitis, the therapeutic efficacy of fingolimod is not only associated with a reduced entry of inflammatory cells into the nervous system, but also with a direct effect mostly on astroglial cells. CONCLUSIONS: In multiple sclerosis patients, the available evidence indicates that fingolimod efficacy is directly associated with impairment of circulation of several T cell subsets and possibly B cells. Animal studies raise the possibility that an additional effect on glial cells might also contribute to the clinical efficacy. SN - 1576-6578 UR - https://www.unboundmedicine.com/medline/citation/22718407/[Basic_mechanisms_of_action_of_fingolimod_in_relation_to_multiple_sclerosis]_ L2 - http://www.revneurol.com/LinkOut/formMedLine.asp?Refer=2012080&Revista=RevNeurol DB - PRIME DP - Unbound Medicine ER -