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Prevention of Vein Graft Intimal Hyperplasia with Optimized Human Apyrase

用优化的人腺苷三磷酸双磷酸酶预防静脉移植物内膜增生

基本信息

批准号：
8391881
负责人：
RIDONG CHEN
金额：
$ 28.16万
依托单位：
APT THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-07 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8391881
关键词：
Acute Adenosine Affect Amino Acid Substitution Angiotensin-Converting Enzyme Inhibitors Anti-Inflammatory Agents Anti-inflammatory Applications Grants Apyrase Arterial Injury Aspirin Attenuated Blood Circulation Blood Platelets Blood Vessels Blood flow Bypass Caliber Cell Line Cells Chinese Hamster Ovary Cell Clinical Coronary Coronary Artery Bypass Data Deposition Development Dose Economic Burden Endothelial Cells Endotoxins Enzymes Failure Family suidae Generations Goals Hemorrhage Hemostatic function Human Hyperplasia Immune Infiltration Inflammation Lesion Leukocytes Licensing Lipids Liquid substance Lung Transplantation Marketing Modeling Mus Myocardial Ischemia Nucleotides Operative Surgical Procedures Organ Transplantation Outcome Pathology Patients Peripheral Phase Plasma Prevention Process Publishing Rattus Regimen Reporting Risk Saphenous Vein Small Business Innovation Research Grant Stress Therapeutic Therapeutic Agents Thrombosis Tissues Translating Tunica Media Veins base clopidogrel commercial application cytokine effective therapy extracellular graft failure graft function improved in vivo macrophage migration neointima formation novel therapeutics percutaneous coronary intervention prevent receptor research clinical testing response social standard of care therapeutic development vascular inflammation vascular smooth muscle cell migration vascular smooth muscle cell proliferation

项目摘要

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 many new 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 human enzyme 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 I SBIR 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 and peripheral bypass surgery patients.

描述（由申请人提供）：隐静脉是冠状动脉搭桥术和外周搭桥术中最常用的移植物，但通畅性较差。15-20%的移植物在第一个月失败，大约25%在第一年失败。早期静脉移植物闭塞通常是由于血栓形成，而晚期失败通常是由于新生内膜增生，一种发生在暴露于动脉循环的静脉中的病理适应过程。近几十年来，已经开发了许多新的治疗药物，试图改善静脉移植物的通畅性，但没有一个转化为临床实用性。因此，新生内膜增生的问题仍然是患者和临床医生都不能接受的。APT 102是一种优化的人酶，其水解细胞外促血栓形成ADP和促炎ATP，并最终导致体内抗炎腺苷的产生。SBIR第一阶段拨款申请的目的是确定小鼠静脉移植手术中APT 102的长期抗新生内膜作用。最终目标是开发基于腺苷三磷酸双磷酸酶的治疗作为冠状动脉和外周搭桥手术患者的标准治疗。公共卫生关系：该I期SBIR资助申请的目的是确定优化的人腺苷三磷酸双磷酸酶在小鼠静脉移植手术中的长期抗新生内膜作用。最终目标是开发基于腺苷三磷酸双磷酸酶的治疗作为冠状动脉和外周搭桥手术患者的标准治疗。