SBIR Phase I: Developing a Novel In Vitro Assay Using Patient-derived Cardiomyocytes To Screen for Drugs To Treat Hypertrophic Cardiomyopathy

SBIR 第一阶段：开发一种新型体外检测方法，利用患者来源的心肌细胞筛选治疗肥厚性心肌病的药物

• 批准号: 1548305
• 负责人: Jason Lam
• 金额: $ 15万
• 依托单位: Stem Cell Theranostics, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1548305&HistoricalAwards=false
• 关键词: SBIR; Phase; Developing; Novel; Vitro

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop a stem cell-based platform to screen drugs for treating hypertrophic cardiomyopathy (HCM). The global economic burden of heart failure is a staggering $110B per year, touching the lives of nearly everyone. Stem cell-derived disease models enable us to innovate in the heart failure space in a way that has not been possible before. The ability to generate induced pluripotent stem cells from normal and diseased populations will enable the development of authentic preclinical disease models. These cell lines will contribute to a better understanding of cardiac disease, and will expedite the development of new and better drugs to treat the disease. This platform also will enable the understanding of cardio-toxic impact of any drug, which is a major problem for drug attrition in clinical trials. The market potential for novel drug discovery, which is enabled by this technology, allows access to the multi-billion dollar drug discovery market.This SBIR Phase I project proposes to establish the technical foundation for an in-vitro platform to screen for drugs to treat HCM. The goal is to address how select therapies with known results in animal models affect the morphology and function of cardiomyocytes generated from a library of clinically defined HCM genotypes. Preliminary results have demonstrated that the cardiomyocyte models mimic disease phenotypes, and that these phenotypes can be partially rescued. The work in this project will build on these preliminary findings and move the platform from an academic interest into an industrial technology. As with any new platform, developing standard processes can be a barrier for adoption, especially when that technology involves the complexity inherent in biological systems. The plan is to adapt high content imaging and multi-electrode array technologies to assess structural characteristics, calcium cycling, and electromechanical functions of the cardiomyocytes. Then, the platform will be used to screen a set of 11 drugs for their ability to rescue disease phenotypes. This work will demonstrate that the cardiac disease models are a valid preclinical drug screening technology to evaluate genotype-specific therapy for treatment of HCM.

这个小型企业创新研究(SBIR)项目的更广泛的影响/商业潜力是开发一个基于干细胞的平台来筛选治疗肥厚型心肌病(HCM)的药物。全球每年因心力衰竭造成的经济负担高达1100亿美元，影响到几乎每个人的生活。干细胞衍生疾病模型使我们能够在心力衰竭领域以一种以前不可能实现的方式进行创新。从正常和疾病人群中产生诱导多能干细胞的能力将使真正的临床前疾病模型的开发成为可能。这些细胞系将有助于更好地了解心脏病，并将加快开发更好的新药来治疗这种疾病。这个平台还将使人们能够了解任何药物的心脏毒性影响，这是临床试验中药物磨损的主要问题。这项技术带来的新药发现的市场潜力使人们能够进入数十亿美元的药物发现市场。这项SBIR第一阶段项目建议为体外平台筛选治疗肥厚性心肌炎的药物奠定技术基础。其目标是解决动物模型中已知结果的选择疗法如何影响从临床定义的HCM基因型库产生的心肌细胞的形态和功能。初步结果表明，心肌细胞模型模拟了疾病的表型，这些表型可以部分挽救。该项目的工作将建立在这些初步发现的基础上，并将该平台从学术兴趣转变为工业技术。与任何新平台一样，开发标准流程可能会成为采用的障碍，特别是当该技术涉及生物系统固有的复杂性时。该计划将采用高含量成像和多电极阵列技术来评估心肌细胞的结构特征、钙循环和机电功能。然后，该平台将被用于筛选一组11种药物的拯救疾病表型的能力。这项工作将证明心脏病模型是一种有效的临床前药物筛选技术，用于评估针对HCM的基因特异性治疗。