Adjunctive Use of Apyrase to Fibrinolytic Therapy

描述（由申请人提供）：人apyrase是一种非常有前途的治疗急性心肌梗死的疗法。这种酶强烈抑制血小板的激活和聚集，有适度的出血风险。利用蛋白质信息学方法，我们成功地设计了具有抗血小板和抗炎活性的人类apyrase。在I期临床试验的支持下，我们将确定优化的人用酶与tPA联合是否能在不增加出血风险的情况下诱导冠状动脉快速持续再通。公共卫生相关性：我们将利用狗的冠状动脉血栓形成模型来验证人用apyrase是否比氯吡格雷更有效地改善冠状动脉通畅而不增加出血风险。

DESCRIPTION (provided by applicant): Human apyrase represents a highly promising therapy for treatment of acute myocardial infarction. This enzyme strongly inhibits platelet activation and aggregation with modest bleeding risk. Using a protein informatics approach, we have successfully engineered human apyrases which exhibit both antiplatelet and anti-inflammatory activities. With the Phase I grant support, we will determine whether optimized human apyrases, in combination with tPA, induce rapid and sustained coronary artery recanalization without increasing bleeding risk. PUBLIC HEALTH RELEVANCE: We will utilize a coronary thrombotic model in dogs to validate whether human apyrase more effectively improve coronary patency than clopidogrel without increasing bleeding risk.