Prevention of Vein Graft Intimal Hyperplasia with Optimized Human Apyrase

DESCRIPTION (provided by applicant): The saphenous vein is the most commonly used graft for coronary artery bypass and peripheral bypass surgery, but has poor patency. 15-20% grafts fail in the first month and approximately 25% in the first year. Early vein graft occlusion is typically due to thrombosis, while late failures typically result from neointimal hyperplasia, a pathological adaptation process that occurs in veins exposed to the arterial circulation. Recent decades have seen the development of manynew therapeutic agents to try to improve vein graft patency, but none has translated into clinical utility. Consequently, the problem of neointimal hyperplasia continues to remain unacceptable to patients and clinicians alike. APT102 is an optimized humanenzyme that hydrolyzes extracellular prothrombotic ADP and proinflammatory ATP and ultimately leads to generation of anti- inflammatory adenosine in vivo. The goal of this Phase I SBIR grant application is to determine the long-term anti-neointimal effects of APT102 in the setting of vein graft surgery in mice. The ultimate goal is to develop apyrase-based therapy as the standard of care therapy for coronary and peripheral bypass surgery patients. PUBLIC HEALTH RELEVANCE: The goal of this Phase ISBIR grant application is to determine the long-term anti- neointimal effects of an optimized human apyrase in the setting of vein graft surgery in mice. The ultimate goal is to develop apyrase-based therapy as the standard of care therapy for coronary andperipheral bypass surgery patients.