A Novel Lipotherapy to Reduce Infarct Size Following Myocardial Infarction

一种减少心肌梗塞后梗塞面积的新型脂肪疗法

• 批准号: 9767236
• 负责人: Philip Bauer
• 金额: $ 73.6万
• 依托单位: ENDOPROTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9767236
• 关键词: Adverse effects; Area; Arteries; Biological; Blood flow; Cause of Death; Cell membrane; Cells; Centers for Disease Control and Prevention (U.S.); Coronary; Coronary Occlusions; Coronary artery; Data; Dose; Drug Kinetics; Edema; Endothelial Cells; Endothelium; Family suidae; Fibrinolysis; Functional disorder; Glycocalyx; Goals; Heart; Hemorrhage; Histopathology; Infarction; Infiltration; Inflammation; Infusion procedures; Ischemia; Lead; Left ventricular structure; Leukocytes; Life; Lipids; Modeling; Mus; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardium; Oryctolagus cuniculus; Outcome; Patients; Perfusion; Phase; Plug-in; Production; Protocols documentation; Randomized Clinical Trials; Reperfusion Injury; Reperfusion Therapy; Risk; Safety; Swelling; Symptoms; Testing; Therapeutic; Therapeutic Embolization; Thioflavin S; Time; Toxic effect; Treatment Efficacy; Vesicle; base; cell type; clinical practice; effective therapy; endothelial dysfunction; novel; novel therapeutic intervention; novel therapeutics; percutaneous coronary intervention; phase 1 study; recruit; regenerative; sex

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.

根据CDC在2013年的数据，缺血性心脏病是全球死亡的主要原因， 美国约有45万患者死于缺血性心脏病。它在临床实践中得到了很好的确立 通过经皮冠状动脉介入治疗（PCI）使梗死相关动脉（伊拉）再通 提高ST段抬高型心肌梗死患者的心肌挽救率和预后 （STEMI）。当缺血持续时间超过症状出现后1小时时，再灌注损伤 PCI经常由于微血管中的“无复流”现象而导致梗死扩大。 “危险区”。认为多种机制导致“无复流”，并且没有有效的治疗方法来治疗“无复流”。 改善再灌注期间的“无复流”和梗死扩大， STEMI和PCI后的临床试验。EndoProtech公司开发了一种新的治疗方法 在PCI过程中改变内皮细胞（EC）的脂质含量，这对PCI的稳定性有影响。 微血管内皮细胞，并改善再灌注过程中“危险区域”的“无复流”。整体 本项目的目的是证明我们的治疗在增强心肌细胞功能方面的安全性和有效性。 STEMI和PCI后的抢救。第二阶段的目标是：1。评价治疗的有效性 减少“无复流”和梗死面积; 2.描述治疗对再生/修复的影响 参与MI后早期重塑的细胞; 3.进行治疗的药代动力学研究;和4. 确定治疗在各种储存条件下的稳定性。成功实现这些目标将 确定：a）在PCI期间输送时我们的治疗的有效剂量，B）治疗对 风险区域中的“无复流”，以及c）用于最佳生产和更长的治疗保存期的方案。 目的与将为FDA新药申请提供部分支持的研究一致。