Alison Easter, PhD, from Biogen Idec, Discovery Toxicologist, will discuss the outcomes of a study that evaluated two human iPS (induced pluripotent stem cell)-derived cardiac myocyte assays with the aim of bridging the gap between high-throughput, recombinant cell-based assays and the in vivo telemetry study.
Andrew Bruening-Wright, PhD, Principal Scientist at ChanTest, will provide a comprehensive overview on the evaluation of contractile activity of stem cell-derived human cardiomyocytes using MEA and impedance analysis.
The potential value of human iPS-derived cardiac myocytes in preclinical safety assessment
Cardiac safety is usually assessed in early preclinical discovery by determining the effects of compounds on ion channels known to play key roles in the formation of the cardiac action potential, a critical component of cardiac function.
However, the net physiological effect of activity at multiple ion channels (or other off targets) cannot be assessed and it is difficult to predict potential in vivo effects. This is typically addressed in a large animal in vivo telemetry study which can detect drug-induced changes in cardiovascular parameters including heart rate, blood pressure and ECG intervals.
These in vivo studies are expensive and resource intensive, limiting use in early phase programs.
The aim of this study was to evaluate two human iPS (induced pluripotent stem cell)-derived cardiac myocyte assays, with the aim of bridging the gap between high-throughput, recombinant cell-based assays and the in vivo telemetry study.
We assessed the effects of 18 test compounds in a multi-electrode array electrophysiology (MEA) assay and an impedance assay (xCELLigence), both assays were conducted at ChanTest, OH, USA. These assays allow measurement of a number of parameters thought to be associated with various in vivo cardiovascular endpoints.
These 18 compounds were selected to cover a wide range of hERG, Cav1.2 and Nav1.5 ion channel activity. Data were analyzed to determine whether ion channel “fingerprints” were associated with specific cardiovascular endpoints and could indicate the risk of discrete cardiovascular events in vivo.
The data, recommendations for further study, and potential use in preclinical safety assessment will be discussed in this webinar.
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Andrew Bruening-Wright, Ph.D.
Alison Easter, Ph.D.
Discovery Toxicologist, Preclinical Safety Department
Dawn Van Dam
President & CEO
One Million Solutions in Health™