Abstract
Drug-induced arrhythmia has been a major cause of drug development failure and the market withdrawal of novel compounds. Of particular concern is the block of the ion channel IKr (hERG) by drugs which can result in torsades de pointes (TdP), a dangerous ventricular fibrillation. Unanticipated toxic effects on contractility such as with the tyrosine kinase inhibitors and anthracyclines are also of increasing concern.
Human iPSC-derived cardiomyocytes (hiPSC-CMs) offer the opportunity to screen drugs in vitro using a more physiologically relevant model that expresses multiple ion channels and spontaneously contracts.
Until recently, ICH guidelines have favored animal models and hERG overexpression lines to assess the cardiac safety of investigational new drugs. The Comprehensive in vitro Proarrhythmia (CiPA) initiative utilizes human iPSC-derived cardiomyocytes as a more complex physiologically relevant model to investigate compound effects on multiple ion channels in vitro.
