Method for in vitro detection of the proarrhythmogenic risk of a drug candidate on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)

摘要

This patent relates to a method of detecting in vitro the proarrhythmogenic risk of a drug candidate performed on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), where the experimental measurements and recordings of at least five ion currents and of externally paced action potentials (AP) are carried out on a high-performance automated patch-clamp platform before and after application of the candidate drug, and an advanced cardiomyocyte electrophysiology mathematical model is used to accurately reproduce the shape of experimentally recorded externally paced action potential and to generate a restauration stimulus file including the sum of ion currents inhibited by the drug to be applied to the hiPSC-CM in order to restore the initial externally paced action potential, and further used to compute metrics predictive of said proarrhythmogenic risk.