12.09.2018 | Webinar: CiPA study: Bridging ion channel and myocyte data
CardioExcyte 96, Patchliner and SyncroPatch 384PE Webinar
Date: September 12, 4:00 PM CEST (10:00 AM EDT)
Get up-to-date with the CiPA progress of the Myocyte and Ion Channel Work Goups:
- CiPA myocyte phase II validation study results: cross-site comparison using the CardioExcyte 96
- HTS Phase I study: an update on progress of the CiPA Ion Channel Work Stream using the SyncroPatch 384PE and Patchliner
Dr. Sonja Stölzle-Feix
Director Scientific Affairs, Nanion Technologies and member of the ion channel screening sub-team of the CiPA initiative
Nanion Technologies GmbH, Germany
CiPA myocyte phase II validation study results: cross-site comparison using the CardioExcyte 96
Since 2005 the S7B and E14 guidances from ICH and FDA have been in place to assess a potential drug candidate's ability to cause long QT syndrome. To refine these guidelines, the FDA proposed the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, where the assessment of drug effects on cardiac repolarization was one subject of investigation. Within the myocyte validation study, effects of pharmaceutical compounds on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were assessed and this article will focus on the evaluation of the proarrhythmic potential of 23 blinded drugs in four hiPSC-CM cell lines.
Experiments were performed on the CardioExcyte 96 at different sites. A combined readout of contractility (via impedance) and electrophysiology endpoints (field potentials) was performed.Our data demonstrates that hERG blockers such as dofetilide and further high risk categorized compounds prolong the field potential duration. Arrhythmia were detected in both impedance as well as field potential recordings. Intermediate risk compounds induced arrhythmia in almost all cases at the highest dose. In the case of low risk compounds, either a decrease in FPDmax was observed, or not a significant change from pre-addition control values.
With exceptions, hiPSC-CMs are sensitive and exhibit at least 10% delayed or shortened repolarization from pre-addition values and arrhythmia after drug application and thus can provide predictive cardiac electrophysiology data. The baseline electrophysiological parameters vary between iPS cells from different sources, therefore positive and negative control recordings are recommended.
Senior Application Scientist
Nanion Technologies Inc., USA
HTS Phase I study: an update on progress of the CiPA Ion Channel Work Stream using the SyncroPatch 384PE and Patchliner
"The CiPA HTS Ion Channel Working Group finalized its phase I study in 2017. Amongst other external sites, Nanion Technologies in Germany, USA and Japan participated with the Patchliner and the SyncroPatch 384PE in this study. A comparative view of the ion channel targets and a cross-platform and cross-site comparison will be presented. Furthermore, results from the myocyte Work Stream using arrhythmogenic compounds will be compared and confirmed with patch clamp data derived from the HTS Work Stream.“
Please note: The original webinar presentation contained 8 slides with data of an upcoming publication. Due to confidentiality reasons, the relevant slides were cut out of the movie.