Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
Int J Neurosci. 2013 Mar;123(3):163-9. doi: 10.3109/00207454.2012.749255. Epub 2012 Dec 21.
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.
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.
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).
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.
FTY720（fingolimod）是一种已知的鞘氨醇-1-磷酸（S1P）受体激动剂，已在临床试验中用于治疗多发性硬化症、肾移植以及减少心脏、肝脏和肾脏的再灌注损伤。这些临床试验大多显示出积极的效果。特别是 MS 的临床试验表明，FTY720 治疗组的复发率降低。现在，一些动物实验表明，FTY720 通过 S1P1 介导的抗凋亡机制发挥神经保护作用，可能成为治疗中风患者的新化合物。它在动物身上是否有效尚不清楚，因此我们进行了系统评价以明确这一点。
我们通过电子和手动搜索文献，对 FTY720 在局灶性脑缺血动物模型中的疗效进行了系统评价和荟萃分析。提取研究质量、FTY720 剂量、给药时间和以梗死体积或功能缺陷为测量指标的结果数据。所有研究的数据均采用标准化均数差荟萃分析进行分析。
在确定的 19 项研究中，有 9 项被纳入。在所有纳入的研究中，有 178 只动物用于计算梗死体积，有 194 只动物用于评估神经功能缺损。根据已发表的 11 项质量评分标准，这些研究的方法学质量范围为 2 至 10 分。在选择的 9 项研究中，只有一项报告了 FTY720 的阴性结果。该结果表明，FTY720 减少了梗死体积（SMD = -1.31，95%CI -1.99 至 -0.63）并改善了功能结局（SMD = -1.61，95%CI -2.17 至 -1.05）。
我们纳入的数据支持 FTY720 是一种治疗中风的候选药物，但应谨慎考虑。未来应进行更多高质量的实验研究，以评估 FTY720 的安全性。还应考虑 FTY720 在模拟糖尿病和高血压等合并症的老年动物中的有效性。
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