Human Cardiac Chip for Assessment of Proarrhythmic Risk
Grant Award Details
Grant Type:
Grant Number:
DISC2-10090
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$899,581
Status:
Closed
Progress Reports
Reporting Period:
NCE
Grant Application Details
Application Title:
Human Cardiac Chip for Assessment of Proarrhythmic Risk
Public Abstract:
Research Objective
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.
Impact
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
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.
Impact
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.
Statement of Benefit to California:
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.
Publications
- Front Pharmacol (2021): Heart Muscle Microphysiological System for Cardiac Liability Prediction of Repurposed COVID-19 Therapeutics. (PubMed: 34421592)
- 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)
- Clin Transl Sci (2021): In vitro safety “clinical trial” of the cardiac liability of drug polytherapy. (PubMed: 33786981)
- bioRxiv (2020): In Vitro Safety “Clinical Trial” of the Cardiac Liability of Hydroxychloroquine and Azithromycin as COVID19 Polytherapy. (PubMed: 33398282)