A Novel Lipotherapy to Reduce Infarct Size Following Myocardial Infarction

根据美国疾病控制与预防中心2013年的数据，缺血性心脏病是全球主要的死亡原因， 美国约有45万名患者死于缺血性心脏病。它在临床实践中得到了很好的证实。 经皮冠状动脉介入治疗(PCI)对梗塞相关动脉(IRA)的再通 改善ST段抬高心肌梗死患者的心肌挽救和预后 (STEMI)。当缺血持续时间从症状出现之日起超过1h时，再灌注损伤 经皮冠状动脉介入治疗常因微血管“无复流”现象而导致梗塞扩大。 “危险区域”。有多种机制被认为是导致“无复流”的原因，目前尚无有效的治疗方法。 在大规模随机试验中发现再灌注期“无复流”和脑梗塞扩大的改善 STEMI和PCI术后的临床试验。EndoProtech，Inc.开发了一种新的治疗方法 这会改变介入治疗期间内皮细胞(ECs)的脂质含量，从而对 微血管内皮细胞和改善再灌流期间“危险区域”的“无复流”。整体而言 该项目的目标是证明我们的治疗方法在增强心肌梗死方面的安全性和有效性。 STEMI和PCI后的抢救。这项第二阶段计划的目的是：1.评估治疗效果 在减少“无复流”和脑梗塞面积方面；2.描述治疗对再生/修复的影响 参与心肌梗死后早期重构的细胞；3。进行治疗的药代动力学研究；以及4。 测定药物在不同储存条件下的稳定性。这些目标的成功实现将 确定：a)我们的治疗在经皮冠状动脉介入治疗期间的有效剂量，b)治疗对 风险区域的“无复流”，以及c)最佳生产和更长保质期的治疗方案。 AIMS与将为FDA的新药申请提供部分支持的研究是一致的。

According to the CDC in 2013, ischemic heart disease is the leading cause of death worldwide, and in the US approximately 450,000 patients died of ischemic heart disease. It is well established in clinical practice that recanalization of the infarct related artery (IRA) using percutaneous coronary intervention (PCI) enhances myocardial salvage and outcomes in patients with ST-segment elevation myocardial infarction (STEMI). When the duration of ischemia exceeds 1 h from onset of symptoms, reperfusion injury following PCI often leads to infarct expansion due to the “no-reflow” phenomenon in the microvasculature of the “area at risk”. Multiple mechanisms are thought to contribute to “no-reflow”, and no effective treatment to ameliorate “no-reflow” and infarct expansion during reperfusion has been identified in large randomized clinical trials following STEMI and PCI. EndoProtech, Inc. has developed a novel therapeutic approach that alters the lipid content of endothelial cells (ECs) during PCI, which has a stabilizing effect on the microvascular endothelium and ameliorates “no-reflow” in the “area at risk” during reperfusion. The overall goal of this project is to demonstrate the safety and efficacy of our therapy in enhancing myocardial salvage following STEMI and PCI. The aims of this Phase II proposal are: 1. Evaluate efficacy of therapy in reducing “no-reflow” and infarct size; 2. Characterize the effect of the therapy on regenerative/reparative cells involved in early post-MI remodeling; 3. Perform pharmacokinetic studies of therapy; and 4. Determine stability of therapy under various storage conditions. Successful completion of these aims will determine: a) the effective dose of our therapy when delivered during PCI, b) the effect of the therapy on ‘no-reflow” in the area at risk, and c) protocols for optimal production and longer shelf life of the therapy. Aims are consistent with studies that will provide partial support for a new drug application to the FDA.