Computational prediction of drug response in short QT syndrome type 1 based on measurements of compound effect in stem cell-derived cardiomyocytes

摘要: Short QT (SQT) syndrome is a genetic cardiac disorder characterized by an abbreviated interval of the patient9s electrocardiogram. The associated with increased risk arrhythmia and sudden death can arise from number ion channel mutations. Cardiomyocytes derived induced pluripotent stem cells generated SQT patients (SQT hiPSC-CMs) provide promising platforms for testing pharmacological treatments directly in human exhibiting mutations specific syndrome. However, difficulty posed relative immaturity hiPSC-CMs, possibility that drug effects observed hiPSC-CMs could be very different corresponding drug effect in vivo.  In this paper, we apply multistep computational procedure translating measured these to response. This process first detects on individual channels based measurements then uses results estimate ventricular action potentials intervals adult patients. We find that able identify IC50 values line four drugs quinidine, ivabradine, ajmaline mexiletine. In addition, predicted effect quinidine good agreement Consequently, appears useful tool helping predicting responses pure vitro patient cell lines.