View All Posters

P2019
QT Prolongation Assay Using Beating Cardiomyocyte Derived From Monkey ES Cell
Presenter Yasuyuki Asai, ReproCELL, Inc., Japan
Additional Authors: Michiyoshi Saito, Akiko Hotta, Thomas Meyer
Drug-induced QT interval prolongation is now a major concern in safety pharmacology. To avoid the risk of drug-induced QT interval prolongation, the assessment of drug candidate in vitro electrophysiological properties is mandatory to envisage appropriate cell-based assay. In this poster, we report cardiomyocytes derived from monkey embryonic stem cells (mESC) constitute a promising cell source for the QT prolongation assay in drug discovery. A novel technique using cardiomyocyte derived from mESC on micro-electrode arrays (MEA) was used to study reference compounds with a reported QT interval prolonging effect. These compounds were E4031, astemizole, rofecoxib, dofetilide, flecainide, lidocaine, quinidine, terfenadine sotalol, and verapamil. All compounds except verapamil a typical false positive when using the hERG indicated a significant prolongation of the field potential. Verapamil, did not show the field potential prolongation using their cells. Whereas the heterologous hERG assay limits cardiac depolarization to just one channel, the mESC assay could reflect native mechanisms involved in cardiac action potential regulation. In addition, large number of cardiomyocytes derived from mESC can be supplied to this system easily, and this system provides the results within 10 minutes without skill. In conclusion, combination of cardiomyocytes derived from mESC and MEA apparatus is effective tool of prediction of QT prolongation effect of compounds from early to late stage of drug discovery.