NA-1神經保護性治療於急性缺血性腦中風的發展進程

An Ongoing Journey of NA-1 for Acute Ischemic Stroke

蔡力凱(Li-Kai Tsai)

《台灣中風醫誌》 3卷2期 (2021/06) Pp. 83-89

https://doi.org/10.6318/FJS.202106_3(2).0002

摘要

神經保護性治療可促進神經細胞存活，有機會成為急性缺血性腦中風之重要治療方向。Nerinetide（NA-1）透過干擾NMDA受器和PSD-95的互動，以降低其下游神經興奮性毒性的發生。於大鼠、小鼠及獼猴之腦中風動物模式，NA-1治療可顯著減少中風範圍和增進神經功能性預後。於ENACT第二期臨床試驗顯示，在準備接受經動脈顱內動脈瘤栓塞術治療的病人，NA-1治療可減少術中缺血性中風的病灶個數（發生比率0.53,95%信賴區間0.38－0.74），且無嚴重之副作用。而後之ESCAPE-NA1第三期臨床試驗，收集了1,105位罹患急性缺血性中風且接受了經動脈血栓移除術之病患，研究發現NA-1治療組之擁有三個月較佳預後的病人比例和對照組相似（61.4%vs.59.2%），然而次級分析中若僅分析未接受rt-PA的病人，可發現經NA-1治療可獲得較佳的預後（風險比1.18,95%信賴區間1.01－1.38）。ESCAPE-NEXT為一進行中的第三期隨機對照雙盲臨床試驗，將收錄經動脈血栓移除術治療的急性缺血性中風患者，但受試者不可接受rt-PA血栓溶解治療，研究結果值得期待。

關鍵字

臨床試驗 ； 神經興奮性毒性 ； NA-1 ； 神經保護

並列摘要

Neuroprotection may be an important therapeutic direction for acute ischemic stroke through maintaining cell viability. Nerinetide (NA-1) disrupts the interaction between NMDA receptor and postsynaptic density protein 95, leading to reduction of downstream neurotoxic signaling. The preclinical studies have demonstrated the functional and pathological benefits of NA-1 treatment in rodents and non-human primates with transient focal cerebral ischemia. In the phase 2 ENACT trial, NA-1 treatment reduced number of cerebral embolic infarcts (adjusted incidence rate ratio 0.53, 95% CI 0.38-0.74) after endovascular aneurysm repair without serious adverse events. In the phase 3 ESCAPE-NA1 trial, patients with acute ischemic stroke preparing to undergo endovascular thrombectomy (EVT) were randomly assigned to receive NA-1 (n = 549) or placebo (n = 556) within time widow of 12 hours after stroke onset. Three months after stroke, the overall efficacy and safety outcomes were similar between NA-1 and placebo groups with percentage of favorable outcome of 61.4% and 59.2%, respectively (p = 0.35). However, among patients who were not treated with concomitant alteplase, patients received NA-1 had better functional outcome than controls (risk ratio, 1.18; 95% CI, 1.01-1.38). The ESCAPE-NEXT trial is ongoing to test the efficacy of NA-1 in patients with acute ischemic stroke receiving EVT excluding pharmaceutical thrombolysis and the results are anticipated.

並列關鍵字

clinical trial ； excitotoxicity ； NA-1 ； neuroprotection