Combination Treatment of tPA and Apyrase for Stroke

描述（由申请人提供）：人apyrase是一种非常有前途的治疗急性缺血性中风的方法，急性缺血性中风是导致死亡和残疾的主要原因，对大多数患者几乎没有有效的治疗方法。利用蛋白质信息学方法，我们成功地设计了一种人类apyrase，它比野生型apyrase具有更高的酶活性和血小板抑制作用。重要的是，优化后的apyrase在预防脑出血的同时，对实验性脑卒中具有脑保护作用。在II期资助的支持下，我们将确定apyrase治疗是否比阿司匹林和GPIIb/IIIa受体拮抗剂联合r-tPA治疗卒中闭塞溶栓更有效，同时出血风险更低。

DESCRIPTION (provided by applicant): Human apyrase represents a highly promising therapy for acute ischemic stroke which is a leading cause of death and disability with almost no effective therapy for most patients. Using a protein informatics approach, we have successfully engineered a human apyrase which exhibits significantly higher enzymatic activity and platelet inhibition than the wild-type apyrases. Importantly, the optimized apyrase conferred cerebroprotection against experimental stroke while preventing intracerebral hemorrhage. With the Phase II grant support, we will determine whether apyrase therapy is more effective while having lower bleeding risk than aspirin and a GPIIb/IIIa receptor antagonist, in combination with r-tPA for thrombolysis of stroke occlusion. PUBLIC HEALTH RELEVANCE: We will utilize clinically relevant embolic stroke models in rats to validate whether human apyrase improves efficacy and reduce cerebral hemorrhage associated with thrombolytic treatment of ischemic stroke.