Discovery and Development of Therapeutic Genes for CHF

CHF 治疗基因的发现和开发

• 批准号: 8743232
• 负责人: H. Kirk Hammond
• 金额: $ 291.78万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8743232
• 关键词: Animal Model; Attenuated; Basic Science; Calcium; Candidate Disease Gene; Cardiovascular Diseases; Clinical; Clinical Treatment; Clinical Trials; Congestive Heart Failure; Development; Discipline; Environment; Functional disorder; Gene Transfer; Goals; Heart; Heart failure; Mission; Mitochondria; Modeling; National Heart, Lung, and Blood Institute; Physicians; Physiology; Production; Program Research Project Grants; Proteins; Regulatory Pathway; Research; Science; Scientist; System; Testing; Therapeutic Agents; Translational Research; United States National Institutes of Health; clinical application; digital imaging; gene therapy clinical trial; glycosylation; novel therapeutics; pre-clinical; preclinical study; programs; success; therapeutic gene; translational study; vector

The purpose of this Program Project Grant competitive renewal application entitled "Discovery & Development of Therapeutic Genes for CHF" is to enable a number of scientists at VMRF and UCSD to maintain an efficient, interactive and mutually reinforcing program of basic and translational research to promote the discovery and development of therapeutic genes for congestive heart failure (CHF) and other cardiovascular diseases. The Program will facilitate the transition from discovery to clinical application of new therapeutic genes. This model combines discovery research with practical "street-smart" preclinical development. Successfully attaining our goals will require separate but highly integrated Projects that contain the proper proportions f discovery research and focused preclinical development, an accomplished translational physiology Core, and an interactive group of VMRF and UCSD physician-scientists in an ideal environment. Our goals are to identify, perform mechanistic preclinical studies, and eventually to launch clinical trials of promising candidate genes. Strengths of our Program include: i) the breadth of our expertise across disciplines relevant to the goals of the NHLBI; 2) the novelty of approaches ranging from bench science to translational studies using high-fidelity animal models of cardiovascular diseases; and 3) our previous success navigating the regulatory pathway from discovery to launching clinical gene therapy trials. Our Program, which is focused on fundamental mechanisms by which the failing heart can be treated (or heart failure avoided), includes three Projects: Project 1 (Dr. Hammond) will develop and test unique AC-related proteins as therapeutic agents for clinical CHF. Project 2 (Dr. Roth) will focus on the impact of cavelolin-3 and mitochondrial function in the pathophysiology and treatment of CHF; and Project 3 (Dr. Dillmann) will use gene transfer to attenuate adverse glycosylation of calcium-related proteins and resolve mitochondrial abnormalities in CHF. Four Cores will support the Program: Digital Imaging (Dr. Farquhar); Vector Production (Dr. Miyanohara); Translational Systems (Dr. Hammond) and Clinical & Administrative (Dr. Hammond).

这项名为“发现和开发CHF治疗基因”的计划项目资助竞争性更新申请的目的是使VMRF和UCSD的一些科学家能够保持一个有效，互动和相互加强的基础和转化研究计划，以促进充血性心力衰竭（CHF）和其他心血管疾病治疗基因的发现和开发。该计划将促进新的治疗基因从发现到临床应用的过渡。这种模式将发现研究与实际的“街头智能”临床前开发相结合。成功实现我们的目标将需要单独但高度集成的项目，这些项目包含适当比例的发现研究和集中的临床前开发，一个完成的转化生理学核心，以及一个理想环境中的VMRF和UCSD医生科学家的互动小组。我们的目标是确定，进行机制的临床前研究，并最终启动有希望的候选基因的临床试验。我们计划的优势包括：i）我们在与NHLBI目标相关的学科中的专业知识的广度; 2）从实验室科学到使用高保真心血管疾病动物模型的转化研究的方法的新奇;以及3）我们之前成功地导航了从发现到启动临床基因治疗试验的监管途径。我们的项目专注于治疗心力衰竭（或避免心力衰竭）的基本机制，包括三个项目：项目1（哈蒙德博士）将开发和测试独特的AC相关蛋白作为临床CHF的治疗药物。项目2（Roth博士）将重点关注cavelolin-3和线粒体功能在CHF病理生理学和治疗中的影响;项目3（Dillmann博士）将使用基因转移来减弱钙相关蛋白的不良糖基化，并解决CHF中的线粒体异常。四个核心将支持该计划：数字成像（Farquhar博士）;矢量生产（Miyanohara博士）;翻译系统（哈蒙德博士）和临床与行政（哈蒙德博士）。