Reversal of Myocardial Infarction by Localized Stimulation

通过局部刺激逆转心肌梗塞

• 批准号: 8591918
• 负责人: FRANCIS G SPINALE
• 金额: $ 20.76万
• 依托单位: MICRO VIDE, LLC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8591918
• 关键词: Address; Affect; Animal Model; Animals; Area; Beds; Biological; Biological Markers; Caring; Cause of Death; Cicatrix; Clinical; Consultations; Coronary heart disease; Development; Devices; Drops; Effectiveness; Electric Stimulation; Ensure; Epithelial; Extracellular Matrix; Feasibility Studies; Fibroblasts; Frequencies; Future; Harvest; Heart failure; Image; In Vitro; Infarction; Intellectual Property; Lead; Left; Left Ventricular Remodeling; Malignant - descriptor; Matrix Metalloproteinase Inhibitor; Matrix Metalloproteinases; Measures; Medical; Mesenchymal; Modeling; Monitor; Morbidity - disease rate; Myocardial; Myocardial Infarction; Myocardium; Outcome; Pacemakers; Patients; Peptide Hydrolases; Phase; Phenotype; Population; Predisposition; Process; Proteolysis; Readiness; Relative (related person); Reperfusion Therapy; Risk; Safety; Series; Shapes; Small Business Technology Transfer Research; Structure; Techniques; Technology; Technology Transfer; Testing; Therapeutic; Thoracoscopy; Translating; Translations; Treatment Efficacy; Ventricular; Ventricular Remodeling; cell type; design; improved; in vitro testing; in vivo; injured; mortality; novel; novel therapeutics; pre-clinical; programs; prototype; public health relevance; tissue inhibitor of metalloproteinase 4; transdifferentiation

DESCRIPTION (provided by applicant): Heart attacks (i.e. myocardial infarction or MI) occur in more than 1.2 million patients annually. Advances in pharmacological therapy have dramatically improved survival following the initial MI. Consequently, the number of patients with previous MI continues to increase, and as a result, put in jeopardy millions of patients for development of heart failure. In these patients with a previous MI, despite optimal standard-of-care, a scar can form in the portion of the heart muscle (myocardium) that was injured from the MI. Formation of a myocardial scar following MI is associated with a malignant remodeling process with respect to changes in the structure and shape of the MI region (infarct expansion). This adverse remodeling after MI can lead to increased morbidity and mortality in these patients. Unfortunately, there are no current pharmacological / therapeutic means to specifically target the myocardial scar as a means to halt and/or reverse the adverse remodeling post-MI. The technology to be advanced in this application directly addresses this unmet medical need by expanding previously performed proof-of-concept studies whereby localized high frequency stimulation (LHFS) beneficially altered the course of post-MI myocardial remodeling. This fast track technology transfer application is intended to move forward the LHFS technology by finalizing the prototype of this technology, and then optimizing efficacy of this technology in a preclinical animal model of MI. These studies will be undertaken in two phases: Phase I: optimize electrical stimulation parameters for LHFS using a validated in vitro test bed, and Phase II: in vivo testing of a selected LHFS device in a preclinical large animal model of MI. The outcomes from these combined Phase I / Phase II projects will move the LHFS technology to establish readiness for clinical feasibility studies.

描述（由申请人提供）：每年有超过120万患者发生心脏病发作（即心肌梗死或MI）。药物治疗的进步已经显著改善了初始MI后的生存率。因此，患有既往MI的患者数量持续增加，并因此使数百万患者处于心力衰竭发展的危险之中。在这些既往MI患者中，尽管采用了最佳标准治疗，但在MI损伤的心肌（心肌）部分仍可能形成瘢痕。MI后心肌瘢痕的形成与MI区域结构和形状变化（梗死扩展）相关的恶性重塑过程相关。MI后的这种不良重塑可导致这些患者的发病率和死亡率增加。不幸的是，目前还没有特异性靶向心肌瘢痕的药理学/治疗手段作为停止和/或逆转MI后不良重塑的手段。本申请中的先进技术通过扩展先前进行的概念验证研究直接解决了这一未满足的医疗需求，其中局部高频刺激（LHFS）有益地改变了MI后心肌重塑的过程。该快速通道技术转让申请旨在通过最终确定该技术的原型来推进LHFS技术，然后优化该技术在MI临床前动物模型中的疗效。这些研究将分两个阶段进行：第一阶段：使用经验证的体外试验床优化LHFS的电刺激参数，第二阶段：在MI的临床前大型动物模型中对选定的LHFS器械进行体内试验。这些I期/II期项目的成果将推动LHFS技术为临床可行性研究做好准备。