Grant Award Details
To optimize and validate a human “heart on a chip” microphysiological system (MPS) for more accurate drug screening and prediction of proarrhythmic risk
Grant Application Details
- Human Cardiac Chip for Assessment of Proarrhythmic Risk
This proposal will develop patient specific ‘heart-on-a-chip’ devices that will significantly impact early screening of drugs to accurately predict drug-induced proarrhythmia and toxicity.
Patient specific ‘heart-on-a-chip’ device will significantly reduce the cost of bringing a new drug candidate to market while improving efficacy.
Major Proposed Activities
- To improve the maturity of human induced pluripotent stem cell derived cardiac myocytes (hiPSC-CM) in the heart chip.
- To validate the predictive response of the improved cardiac MPS using drugs with known arrhythmia risk.
- To assess the response of drugs with known arrhythmia risk on a cardiac chip with LQT1 hiPSC-CMs.
- To develop a Target Product Profile/Product Concept Document for the cardiac MPS.
We will create a patient specific ‘heart-on-a-chip’ device that will have a significant impact on the development of drugs. A major aspect of this proposal is to establish a heart chip assay to accurately predict drug-induced proarrhythmia and toxicity. If successful, we can reduce the cost and time needed to bring new drugs to market, thereby improving the lives of many Californians and significantly reducing the cost to California's healthcare system.
- Clin Transl Sci (2021) In vitro safety "clinical trial" of the cardiac liability of drug polytherapy. (PubMed: 33786981)
- Front Pharmacol (2021) Heart Muscle Microphysiological System for Cardiac Liability Prediction of Repurposed COVID-19 Therapeutics. (PubMed: 34421592)
- bioRxiv (2020) In Vitro Safety "Clinical Trial" of the Cardiac Liability of Hydroxychloroquine and Azithromycin as COVID19 Polytherapy. (PubMed: 33398282)
- Front Pharmacol (2019) Improved Computational Identification of Drug Response Using Optical Measurements of Human Stem Cell Derived Cardiomyocytes in Microphysiological Systems. (PubMed: 32116671)
- Sci Rep (2018) Inversion and computational maturation of drug response using human stem cell derived cardiomyocytes in microphysiological systems. (PubMed: 30514966)