Apyrase to treat ischemia/reperfusion injury during lung transplantation

描述（由申请人提供）：人腺苷三磷酸双磷酸酶代表了一种非常有前途的预防或减少肺移植期间缺血-再灌注损伤的疗法。这种酶强烈地保护血管完整性，抑制血小板活化和聚集，而不增加出血风险。使用蛋白质信息学方法，我们已经成功地设计了一个优化的人腺苷三磷酸双磷酸酶，APT 102。在II期资助的支持下，我们将确定在大鼠和犬同种异体原位肺移植的临床相关模型中，APT 102是否能改善肺移植物功能而不增加出血风险。最终目标是证明APT 102是否有潜力成为移植相关和其他血管疾病的治疗方法。公共卫生相关性：我们将在大鼠和犬同种异体原位肺移植的临床相关模型中确定人腺苷三磷酸双磷酸酶是否改善肺移植物功能而不增加出血风险。

DESCRIPTION (provided by applicant): Human apyrase represents a highly promising therapy to prevent or reduce ischemia-reperfusion injury during lung transplantation. The enzyme strongly preserves vascular integrity and inhibits platelet activation and aggregation without increasing bleeding risk. Using a protein informatics approach, we have successfully engineered an optimized human apyrase, APT102. With Phase II grant support, We will determine whether APT102 improves lung allograft function without increasing bleeding risk in clinically relevant models of allogeneic orthotopic lung transplantation in rats and dogs. The ultimate goal is to demonstrate whether APT102 has the potential to be a therapy for transplantation-associated and other vascular diseases. PUBLIC HEALTH RELEVANCE: We will determine whether human apyrase improves lung allograft function without increasing bleeding risk in clinically relevant models of allogeneic orthotopic lung transplantation in rats and dogs.