Pivotal Preclinical Studies of Novel Infusible ECM for Treating Acute MI

新型不输 ECM 治疗急性 MI 的关键临床前研究

基本信息

批准号：
10699610
负责人：
Adam M Kinsey
金额：
$ 55.21万
依托单位：
VENTRIX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-15 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10699610
关键词：
Acetylcholine Acute myocardial infarction American Apoptosis Area Arrhythmia Balloon Angioplasty Biocompatible Materials Biological Products Businesses Cardiac Myocytes Catheters Cause of Death Cell Therapy Cells Clinic Clinical Clinical Research Clinical Trials Contracts Coronary Angiography Development Development Plans Echocardiography Eligibility Determination Endothelium Environment Extracellular Matrix Family suidae Fibrosis Geometry Germ Cells Good Manufacturing Process Heart Heart failure Histology Holter Electrocardiography Hydrogels Immunohistochemistry Infusion procedures Injectable Injections Intervention Left Ventricular Remodeling Magnetic Resonance Imaging Marketing Meta-Analysis Metabolism Modeling Myocardial Myocardial Infarction Myocardium Pathway interactions Patients Phase Phase I Clinical Trials Pre-Clinical Model Procedures Rattus Recording of previous events Recurrence Regenerative Medicine Risk Safety Small Business Innovation Research Grant Structure Therapy trial Tissue Engineering Tissues Toxicology Translating Translations United States National Institutes of Health Work commercialization cost comparison heart function improved inflammatory milieu interest ischemic cardiomyopathy manufacture minimally invasive neovascularization novel novel therapeutics patient population phase II trial pre-clinical preclinical study pressure regenerative repaired research study safety assessment standard of care statistics success therapy development

项目摘要

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, leading to a large body of patients suffering 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. While cell therapies have been extensively studied for the treatment of MI and heart failure, meta-analyses of initial cell therapy trials suggest only a modest effect on cardiac function. More recently acellular biomaterials have shown great promise in providing similar or greater functional benefit without the complications associated with cell delivery. 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 cell products. 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. We recently developed a new Infusible ECM, for treating acute MI. We showed it can be delivered to an acute MI via intracoronary infusion and that it improves cardiac function in a rat acute MI model following simulated intracoronary delivery. In our previous studies, we optimized delivery and retention of Infusible ECM and demonstrated preliminary feasibility and efficacy in a porcine acute MI model. The studies proposed in this Phase II project are part of the final steps to initiate studying Infusible ECM in patients, and a key step in bringing a biomaterial product to market, which will be complementary to existing standard of care. This will be the first intracoronary infusible regenerative biomaterial product for treating acute MI patients.

概括心肌后心脏梗死（MI）每年继续成为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，而约200K将有一个经常性的MI，导致大型患有心力衰竭的患者身体。这些惊人的统计数据需要开发新的缺血性心肌病患者的疗法。组织工程和再生医学策略为发展这些患者的新疗法开发提供了巨大的潜力。而细胞疗法有经过广泛研究以治疗MI和心力衰竭，初始细胞疗法试验的荟萃分析仅提示对心脏功能的适度影响。最近的细胞生物材料显示出巨大的希望在提供相似或更大的功能益处的情况下，没有与细胞输送相关的并发症。注射刺激内源修复的生物材料是一种有吸引力的替代方法，因为潜在的疗法仍然可以是通过导管侵入最低侵入性的交付，但可能会脱离架子，并大大降低了成本与细胞产品相比。因此，Centrix专注于无细胞再生医学方法。腹侧在开发可注射的生物材料以治疗缺血性心肌病的过程中有成功的历史。二以前的NIH SBIRS导致了ventrigel批准的IND，可注射的，可降低导管的水凝胶源自脱细胞猪心肌。这导致了最近在患者中成功进行了1阶段临床试验 MI后60天至3年。我们最近开发了一种用于治疗急性MI的新型ECM。我们展示了可以通过冠状体输注传递到急性MI，并改善大鼠急性MI的心脏功能模拟冠状内输送后的模型。在以前的研究中，我们优化了交付和保留不可使用的ECM，并在猪急性MI模型中表现出了初步的可行性和功效。研究在此阶段II项目中提出的是启动患者不可使用的ECM的最后步骤的一部分，A 将生物材料产品推向市场的关键步骤，这将是现有护理标准的补充。这将是第一个用于治疗急性MI患者的冠状动脉内不良再生生物材料。