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

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.