Protein Therapeutics to Prevent Heart Failure Post Myocardial Infarction

描述（由申请人提供）： 本申请的广泛目的是确定内源性心脏肽B型利钠肽（BNP）是用于人急性心肌梗死（AMI）的新型且有效的蛋白质治疗剂，以保护心肌结构和功能，最终降低人心力衰竭（HP）的负担。这项高度转化的研究建立在申请人正在进行的基础和临床研究的基础上，目前得到HL 83231（心肌梗死中的心脏肽）的支持。我们的应用特别利用了这种小的内源性心肌肽在保护心脏免受损伤和促进心脏修复方面的心脏保护特性。我们的治疗策略是基于BNP的新兴生物学，它超越了肾脏作用，包括对心肌细胞和非肌细胞心肌细胞的直接作用。具体目的如下：目的1：收集HL 83231支持的初步人体研究中30天随访后的临床结局数据，以便使用该数据计算P50项目支持的多中心“预防心肌梗死后心力衰竭安全性和疗效试验”的样本量和把握度计算。目标二：组织由科学家和临床专家组成的科学顾问委员会和指导委员会起草多中心“预防心肌梗死后心力衰竭安全性和有效性试验”计划。“我们还将组织数据和安全监测委员会（DSMB）。目标3：聘请临床研究组织（CRO）开始计划拟定的多中心“预防心肌梗死后心力衰竭安全性和疗效试验”的研究中心招募和监管管理，该试验将由F50项目支持。目标4：促使FDA修订我们研究者持有的BNP用于人心肌梗死的IND，以纳入我们的多中心“预防心肌梗死后心力衰竭安全性和有效性试验”，并得到P50项目的支持。我们相信，我们的提案符合C-TRIF P20计划的目标，并加速了有前途的新治疗干预措施（例如BNP治疗AMI）的转化，以减轻未来HF的负担。 相关性（参见说明）：慢性心力衰竭（CHF）是一种具有显著死亡率和发病率的临床综合征，尽管近年来在病理生理学和治疗方面取得了进展。美国心脏协会的最新数据报告，美国的患病率为500万，发病率为550，000例，年死亡率为52，000例，每年的医疗费用总额为280亿美元。这项研究将有助于应对这一健康挑战。

DESCRIPTION (provided by applicant): The broad objective of this application is to establish that the endogenous cardiac peptide B-type natriuretic peptide (BNP) is a novel and efficacious protein therapeutic for human acute myocardial infarction (AMI) to preserve myocardial structure and function reducing ultimately the burden of human heart failure (HP). This highly translational research builds upon ongoing basic and clinical research pursued by the applicants and currently supported by HL83231 (Cardiac Peptides in Myocardial Infarction). Our application specifically takes advantage of the cardioprotective properties of this small and endogenous myocardial peptide in protecting the heart from injury and promoting cardiac repair. Our therapeutic strategy is based upon the emerging biology of BNP, which goes beyond renal actions and includes direct actions on cardiomyocytes and non-myocyte cardiac cells. The Specific Aims are as follows: Aim 1: To collect clinical outcome data beyond the 30 days follow up in the pilot human study supported by HL83231 so as to use this data to calculate sample size and power calculation for the multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial" to be supported by the P50 program. Aim 2: Organize the Scientific Advisory Board and Steering Committee consisting of both scientists and clinical experts to draft the plan for the multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial." We will also organize the Data and Safety Monitoring Board (DSMB). Aim 3: Engage a clinical research organization (CRO) to begin plans for site recruitment and regulatory management of the proposed multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial" that will be supported by the F50 program. Aim 4: To engage the FDA in amending our investigator held IND for the use of BNP in human myocardial infarction to include our multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial" to be supported by the P50 program. We believe that our proposal meets the objectives of the C-TRIF P20 Program and accelerates translation of promising new therapeutic interventions such as BNP for AMI to reduce the burden of future HF. RELEVANCE (See instructions): Chronic heart failure (CHF) is a clinical syndrome with significant mortality and morbidity despite recent advances in the understanding of the pathophysiology and treatment. The latest figures from the American Heart Association reports a prevalence of 5 million with incidence of 550,000 cases, annual mortality of 52,000 and a total cost of 28 billion dollars in healthcare expense per year in the US. This research will aid in addressing this health challenge.