An Innovative Cardioprotective

说明(申请人提供)：心肌梗死(MI)是美国发病率和死亡率的一个重要原因。H2 Relaxin(H2 R)是一种第三阶段临床试验阶段的多肽，具有抗炎和细胞保护活性，可作为再通治疗的辅助药物用于心肌梗塞的治疗。然而，临床给药不仅昂贵得令人望而却步，而且还受到许多后勤问题的困扰。为了充分利用H_2R途径的治疗潜力，同时克服上述缺点，Angion Biomedica Corp.开发了一个可化学合成的H_2R样多肽库。在初步研究中，我们的先导H2 R样肽Ang-4011显示了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作用。该计划的数据将构成全面的SBIR第二阶段计划目标的基础，该计划的目标包括优化Ang-4011在缓释、临床兼容、可生物降解的微球中的释放，评估Ang-4011在伴有共病(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。该计划的总体目标是为表现为心肌梗死的患者带来潜在的有希望的治疗临床试验。 公共卫生相关性：心肌梗死仍然是发病率和死亡率的重要原因。一种可以缩小梗塞面积和挽救心肌的心脏保护剂可以避免过渡到泵衰竭。

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.