Phase II: Percutaneous deliverable biomaterial for treating myocardial infarction

第二阶段：用于治疗心肌梗塞的经皮可输送生物材料

• 批准号: 8592963
• 负责人: Karen L Christman
• 金额: $ 133.95万
• 依托单位: VENTRIX, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8592963
• 关键词: Acute myocardial infarction; Address; Area; Arrhythmia; Biocompatible Materials; Businesses; Cardiac; Cardiac Myocytes; Cardiomyoplasty; Catheters; Cell Transplantation; Cells; Clinic; Clinical; Clinical Research; Clinical Trials; Complex; Complex Mixtures; Contracts; Cues; Deltastab; Development Plans; Echocardiography; Environment; Extracellular Matrix; Extracellular Matrix Proteins; Family suidae; Goals; Heart Transplantation; Heart failure; Histology; Holter Electrocardiography; Immunohistochemistry; Incidence; Injection of therapeutic agent; Left; Left Ventricular Function; Left Ventricular Remodeling; Liquid substance; Marketing; Modeling; Myocardial; Myocardial Infarction; Myocardium; Pathway interactions; Patients; Pharmacologic Substance; Phase; Rattus; Recurrence; Regenerative Medicine; Regimen; Safety; Small Business Innovation Research Grant; Staging; Structure; Technology; Temperature; Time; Tissues; Toxicology; Translating; Translations; United States; Ventricular; Western World; Work; base; commercialization; cost; design; improved; interest; minimally invasive; novel; patient population; polysaccharide peptide; pre-clinical; preclinical study; prevent; public health relevance; regenerative; repaired; research study; scaffold; therapy development; ventricular assist device

DESCRIPTION (provided by applicant): Heart failure following a myocardial infarction (MI) continues to remain a leading killer in the western world. In the United States, the estimated annual incidence of myocardial infarction (MI) is 745,000 new and 410,000 recurrent episodes. There is a critical need to develop new therapies since end-stage heart failure is only treated through heart transplantation or left ventricular (LV) assist devices, and current pharmaceutical regimens do not adequately prevent post-MI negative LV remodeling. As an alternative to total heart transplantation, cellular cardiomyoplasty, or cell transplantation, has been explored for the treatment of MI and heart failure; however, more recently a cellular biomaterials have shown great promise in providing similar functional benefit without the complications associated with cell delivery. Biomaterial products have the key advantages of being off-the-shelf available and relatively inexpensive to manufacture. Existing materials have however been limited since none have been specifically designed for the myocardium, and none mimic the degraded post-MI extracellular matrix (ECM) they are intended to replace. The materials suffer from 1) their inability to be delivered via current catheter technology, and/or 2) their lack of complex, myocardial specific ECM cues, which promote repair. The material used for the Ventrix product is the first example of a myocardial-specific material that can be delivered via catheter to promote repair in the post-MI environment. This material is liquid at room temperature and forms a porous and fibrous scaffold upon injection into the myocardium. We have shown that it promotes cell influx, increases areas of surviving cardiomyocytes, and preserves LV geometry and cardiac function in a rat MI model, and can be delivered through a percutaneous transendocardial approach in a porcine model. In our Phase I SBIR, we demonstrated that VentriGelTM increased cardiac muscle, improved cardiac function, and prevented negative LV remodeling following catheter based delivery in a porcine MI model. The studies proposed in Phase II are part of the final steps to initiate studying VentriGelTM in patients, and a key step i bringing a biomaterial product to market, which will be complementary or mostly parallel to the current MI pharmaceutical market. In Phase II, we will achieve the following two specific aims to reach our goals: 1) To demonstrate an improvement in cardiac function and negative LV remodeling following delivery of VentriGel" post-myocardial infarction and to determine its optimal volume and delivery time window in a porcine acute myocardial infarction model and 2) To assess safety of VentriGel" via toxicology studies required for IND submission to the FDA. The objective of the proposed project is to complete the key preclinical studies for VentriGelTM to translate to the clinic. This will be the first catheter deliverable regenerative biomaterial product for treating the millions of patients suffering from MI.

描述（由申请人提供）：心肌梗塞（MI）后的心力衰竭仍然是西方世界的主要杀手。在美国，心肌梗塞 (MI) 的年发病率估计为 745,000 例新发病例和 410,000 例复发病例。由于终末期心力衰竭只能通过心脏移植或左心室 (LV) 辅助装置来治疗，并且当前的药物治疗方案不能充分预防 MI 后阴性 LV 重塑，因此迫切需要开发新的疗法。作为全心脏移植的替代方案，细胞心肌成形术或细胞移植已被探索用于 治疗心肌梗死和心力衰竭；然而，最近细胞生物材料在提供类似的功能益处且没有与细胞输送相关的并发症方面显示出巨大的前景。生物材料产品具有现成可用且制造相对便宜的主要优势。然而，现有材料受到限制，因为没有一种材料是专门为心肌设计的，也没有一种材料能够模仿它们打算取代的降解的心肌梗死后细胞外基质 (ECM)。这些材料存在以下问题：1) 无法通过当前的导管技术进行输送，和/或 2) 缺乏促进修复的复杂的心肌特异性 ECM 信号。 Ventrix 产品所用的材料是心肌特异性材料的第一个例子，可以通过导管输送以促进心肌梗死后环境中的修复。这种材料在室温下是液体，注入心肌后形成多孔纤维支架。我们已经证明，它可以促进细胞流入，增加存活心肌细胞的面积，并在大鼠心肌梗死模型中保留左心室几何形状和心脏功能，并且可以在猪模型中通过经皮经心内膜途径进行递送。在我们的 I 期 SBIR 中，我们证明了 VentriGelTM 在猪 MI 模型中增加了心肌，改善了心脏功能，并防止了导管输送后的负性左室重构。 II 期提出的研究是在患者中开始研究 VentriGelTM 的最后步骤的一部分，也是将生物材料产品推向市场的关键一步，这将与当前的 MI 药品市场互补或基本平行。在第二阶段，我们将实现以下两个具体目标，以实现我们的目标：1）证明心肌梗塞后施用 VentriGel 后心脏功能和负性左心室重构得到改善，并确定其在猪急性心肌梗死模型中的最佳体积和递送时间窗口；2）通过向 FDA 提交 IND 所需的毒理学研究来评估 VentriGel 的安全性。拟议项目的目标是完成 VentriGelTM 的关键临床前研究，并将其转化为临床。这将是第一个可用于治疗数百万心肌梗死患者的导管输送再生生物材料产品。