Details

Autor(en) / Beteiligte

• McGinley, Marisa P
• Cohen, Jeffrey A

Titel

Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions

Ist Teil von

• The Lancet (British edition), 2021-09, Vol.398 (10306), p.1184-1194

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• The sphingosine 1-phosphate (S1P) signalling pathways have important and diverse functions. S1P receptors (S1PRs) have been proposed as a therapeutic target for various diseases due to their involvement in regulation of lymphocyte trafficking, brain and cardiac function, vascular permeability, and vascular and bronchial tone. S1PR modulators were first developed to prevent rejection by the immune system following renal transplantation, but the only currently approved indication is multiple sclerosis. The primary mechanism of action of S1PR modulators in multiple sclerosis is through binding S1PR subtype 1 on lymphocytes resulting in internalisation of the receptor and loss of responsiveness to the S1P gradient that drives lymphocyte egress from lymph nodes. The reduction in circulating lymphocytes presumably limits inflammatory cell migration into the CNS. Four S1PR modulators (fingolimod, siponimod, ozanimod, and ponesimod) have regulatory approval for multiple sclerosis. Preclinical evidence and ongoing and completed clinical trials support development of S1PR modulators for other therapeutic indications.