Is-26: Human Stem Cells for Cardiac Disease Modeling and Drug Screening


Passier R *,

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In drug discovery and development it is of upmost importance to distinguish target and off-target effects. The process from target discovery to delivery of safe and effective drugs takes many years and is very expensive. The percentage of drugs that actually make it to the market is extremely low. Before drugs reach the market they need to be tested on their safety. This is particularly relevant for the heart where off-target effects can lead to disturbance of the heart rhythm, which may lead to fatal arrhythmias. Many of these drugs act by extending the QT interval, the time between polarization and depolarization in the ventricle, thus, by definition, are potentially high risk since QT extension can itself lead to fatal arrhythmias. Therefore all drugs need to be tested on the prolongation of the QT interval of the action potential. One important goal in preclinical screens is therefore to identify compounds which extend QT. Current in vitro models are artificial whereas results from screenings in different species can not directly be extrapolated to the human situation. It is thought that the use of human cardiomyocytes for screening drugs may provide a more predictable model and could partially replace existing in vitro and in vivo models. Furthermore, we will discuss cardiac disease modelling and the use of cardiomyocytes derived from human stem cells on different classes of drugs and the predictability of these models.