Systematic review and meta-analysis of the efficacy of sphingosine-1-phosphate (S1P) receptor agonist FTY720 (fingolimod) in animal models of stroke.

BACKGROUND AND PURPOSE: FTY720 (fingolimod) is a known sphingosine-1-phosphate (S1P) receptor agonist, which has been used in clinical trials for treating multiple sclerosis, renal transplantation, and decreasing reperfusion injury in heart, liver, and kidney. Most of these clinical trials have showed a positive effect. Especially, the trials of MS showed a reduction of relapse rate in FTY720-treated patients. Now, some animal experiments indicated that FTY720 could be a new compound available treatment for stroke patients by exerting neuroprotection via S1P1 mediated antiapoptotic mechanisms. Whether it could be effective in animals is unclear, so we conducted a systematic review to make it clear.

METHODS: We conducted a systematic review and meta-analysis of the efficacy of FTY720 in animal models of focal cerebral ischemia by electronic and manual searches of the literature. Data on study quality, FTY720 dose, time of administration, and outcome measured as infarct volume or functional deficit were extracted. Data from all studies were analyzed by means of a standardized mean difference meta-analysis.

RESULTS: Of the 19 identified studies, 9 were included. Among all the included studies, 178 animals were calculated for infarct size and 194 animals were assessed of neurological deficits. The methodological quality of the studies ranged from 2 to 10 according to a published 11-item quality scale. Of the nine studies selected, only one reported a negative result of FTY720. The result indicated that FTY720 reduced the infarct volume (SMD = -1.31, 95% CI -1.99 to -0.63) and improve the functional outcome (SMD = -1.61, 95% CI -2.17 to -1.05).

CONCLUSIONS: The data we included supporting FTY720 was a candidate drug for stroke, but it should be considered with caution. More good quality experimental studies should be performed to evaluate the safety of FTY720 in the future. Whether FTY720 is effective in aged animals that mimicked human with comorbidities like diabetes and hypertension should also be deliberated.