New infusible ECM hydrogel for treating acute myocardial infarction

新型可熔ECM水凝胶治疗急性心肌梗死

• 批准号: 9907247
• 负责人: Karen L Christman
• 金额: $ 79.15万
• 依托单位: VENTRIX, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-20 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907247
• 关键词: Acute; Acute myocardial infarction; American; Animals; Apoptosis; Arrhythmia; Balloon Angioplasty; Balloon Occlusion; Biocompatible Materials; Cardiac Myocytes; Cardiomyopathies; Catheters; Cause of Death; Cell Therapy; Cells; Data; Development; Echocardiography; Environment; Extracellular Matrix; Family suidae; Fibrosis; Formulation; Gel; Geometry; Germ Cells; Guidelines; Heart; Heart Transplantation; Heart failure; Histology; Holter Electrocardiography; Hydrogels; Immunohistochemistry; Infarction; Infusion procedures; Injectable; Injections; Intervention; Left; Meta-Analysis; Metabolism; Modeling; Myocardial; Myocardial Infarction; Myocardium; Organ; Particulate; Patients; Phase; Phase I Clinical Trials; Pre-Clinical Model; Rattus; Recording of previous events; Recurrence; Regenerative Medicine; Safety; Small Business Innovation Research Grant; Testing; Therapy trial; Tissue Engineering; Tissues; Translating; United States National Institutes of Health; Ventricular; clinically relevant; cost; heart function; improved; inflammatory milieu; ischemic cardiomyopathy; left ventricular assist device; minimally invasive; neovascularization; new technology; novel; novel therapeutics; particle; patient population; phase II trial; preclinical study; regenerative; repaired; standard of care; statistics; submicron; success; therapy development

Summary Heart failure post-myocardial infarction (MI) continues to be the leading cause of death in the U.S. Each year it is estimated that ~550K Americans will have a new MI, and ~200K will have a recurrent MI and a majority of these patients will suffer from heart failure. These staggering statistics necessitate the development of new therapies for patients with ischemic cardiomyopathy. Tissue engineering and regenerative medicine strategies offer significant potential for the development of novel therapies to treat these patients. Recently, acellular biomaterials have shown great promise in providing functional benefit without the complications associated with other regenerative medicine approaches. Injectable biomaterials that stimulate endogenous repair are an attractive alternative since potential therapies could still be delivered minimally invasively via catheter yet could be off the shelf and have significantly reduced costs compared to other regenerative medicine products, such as cells. Ventrix is therefore focusing on cell-free regenerative medicine approaches. Ventrix has a history of success in developing injectable biomaterials for treating ischemic cardiomyopathy. Two previous NIH SBIRs resulted in an approved IND for VentriGel, an injectable, catheter-deliverable hydrogel derived from decellularized porcine myocardium. This led to a recent successful Phase 1 clinical trial in patients 60 days to 3 years post-MI. The study proposed herein is a key step in bringing a new biomaterial product to market for treating acute MI. This new soluble version of VentriGel can be delivered via intracoronary infusion, which will enable treatment immediately post-MI, unlike the original formulation, which required transendocardial delivery. Herein, we will test the feasibility of translating this new technology by optimizing delivery and evaluating function in a large animal acute MI model. This will be the first intracoronary infusible regenerative biomaterial product for treating acute MI patients.

总结 心肌梗死（MI）后心力衰竭仍然是美国的主要死亡原因。 据估计，约55万美国人将有一个新的MI，约20万将有一个复发性MI和大多数 这些病人会患上心脏衰竭。这些令人震惊的统计数字需要开发新的 缺血性心肌病患者的治疗方法。组织工程与再生医学策略 为开发治疗这些患者的新疗法提供了巨大的潜力。最近，无细胞的 生物材料在提供功能性益处而没有与 其他再生医学方法。刺激内源性修复的可注射生物材料是 因为潜在的治疗仍然可以通过导管微创地输送， 与其他再生医学产品相比， 细胞因此，Ventrix专注于无细胞再生医学方法。文特里克斯有一个历史， 成功开发可注射生物材料用于治疗缺血性心肌病。前两次NIH SBIRs 导致VentriGel获批IND，VentriGel是一种可注射的导管输送水凝胶， 脱细胞猪心肌。这导致了最近在60天至3天的患者中成功的1期临床试验 年后的MI。本文提出的研究是将新的生物材料产品推向市场的关键一步， 治疗急性心肌梗死。这种新型可溶性VentriGel可通过冠状动脉内输注输送， 能够在MI后立即进行治疗，不像原始制剂需要经内分泌递送。 在此，我们将通过优化交付和评估功能来测试翻译这项新技术的可行性 在大型动物急性MI模型中。这将是第一个冠状动脉内可输注再生生物材料产品 用于治疗急性心肌梗死患者