An Innovative Cardioprotective

描述（由申请人提供）：心肌梗死（MI）是美国发病率和死亡率的重要原因，H2松弛素（H2R）是一种III期临床试验阶段的肽，具有抗炎和细胞保护活性，可以作为再通治疗的辅助手段，潜在地用于心肌梗死的治疗。然而，rhH2R的临床管理不仅昂贵，而且受到许多后勤问题的困扰。为了充分利用H2R通路的治疗潜力，同时克服上述缺点，Angion Biomedica公司开发了一个化学合成H2R样肽库。在初步研究中，我们的先导h2r样肽ANG-4011显示出显著的组织保护作用。目前的1期SBIR方案旨在充分优化ANG-4011对实验性心肌缺血再灌注损伤的治疗效果。该项目的数据将构成SBIR II期综合项目目标的基础，其中包括优化ANG-4011以缓释、临床兼容、可生物降解微球的形式给药，评估ANG-4011在伴有合并症（如年龄和糖尿病）的心肌再灌注模型中的治疗效果，以及ANG-4011的安全性/毒理学评估。该项目的总体目标是为心肌梗死患者的临床试验带来潜在的有前途的治疗方法。

DESCRIPTION (provided by applicant): Myocardial infarction (MI) is a significant cause of morbidity and mortality in the U.S. H2 Relaxin (H2R) is a Phase III clinical trial-stage peptide that exhibits both anti-inflammatory and cytoprotective activities which can potentially be harnessed for the treatment of MI via use as adjuvant to recanalization therapy. However, clinical administration of rhH2R is not only prohibitively expensive but also plagued by numerous logistical issues. To fully capitalize on the therapeutic potential of the H2R pathway while overcoming the afore-mentioned shortcomings, Angion Biomedica Corp. has developed a library of chemically synthesizable H2R-like peptides. In preliminary studies, ANG-4011, our lead H2R-like peptide demonstrated significant tissue protective effects. The present Phase 1 SBIR proposal is designed to fully optimize the therapeutic effects of ANG-4011 in experimental myocardial ischemia-reperfusion injury. Data from this program will form the basis for a comprehensive SBIR Phase II program goals for which include optimization of ANG-4011 delivery in sustained-release, clinically compatible, biodegradable microspheres, evaluation of ANG-4011 therapy in myocardial-reperfusion models accompanied by co-morbidities (e.g. age and diabetes) and ANG-4011 safety/toxicology evaluation. The overall objective of this program is to bring potentially promising therapeutic to clinical trials for patients presenting with MI. PUBLIC HEALTH RELEVANCE: Myocardial infarction remains a significant cause of morbidity and mortality. A cardioprotective agent that reduces infarct size and salvages myocardium can avert the transition to pump failure.