Cardiac Safety and CiPA Services
We assess the proarrhythmic liability of your compounds using patch clamp, MEA and live cell imaging methods.
With more than 15 years of experience in the field, we master classic and modern approaches to cardiac safety studies, including standard FDA guideline S7B compliant hERG screening, cardiac ion channels, hiPSC cardiomyocyte studies, and the latest CiPA proposals.
The classical approach for electrophysiology in cardiac safety is defined by the FDA guideline S7B, which recommends manual patch clamp on the hERG ion channel. Building on more than 15 years' experience with traditional early hERG screening using both manual and automated patch clamp for small and big pharma clients, we have taken the next step and developed a range of methods to cover all ion channels that are relevant in cardiac safety using either manual or automated patch clamp.
Thanks to our strong position in the MEA research field, our group has an outstanding experience using MEA technology e.g. in combination with hiPSC cardiomyocytes for cardiac safety studies. For highest throughput, we have established image-based assays using hiPSC cardiomyocytes on the Hamamatsu FDSS/μCell 384-well platform.
Manual and automated patch clamp
We offer manual patch clamp as well as automated patch clamp services. We use the industry leading platform QPatch for ion channel screening. Our cardiac panel of ion channels include all relevant cardiac ion channels defined by the CiPA consortium, including hERG, Nav1.5, Cav1.2, Cav3.2, KvLQT1/minK, Kv4.3, Kir2.1, Kv1.5.
MEA technology on hiPSC cardiomyocytes
Using our 96-well parallelized MEA platform, we are able to investigate wanted and adverse effects of compounds on cardiac function. Readout parameters include beat rate changes, alterations of the field action potential (“QT-interval in vitro”) and (pro-)arrhythmic assessment. Additionally, this platform allows electrical pacing of the cells.
Live cell imaging on hiPSC cardiomyocytes
Cardioactive compound effects can also be observed in our high-speed Hamamatsu FDSS/μCell test system, using intracellular calcium dynamics as surrogate to assess alterations of field action potential duration and to investigate the arrhythmic beating behavior. This system is capable to run 384-well parallelized experiments.
We are proud to be the EU core site of CiPA
CiPA (the Comprehensive in Vitro Proarrhythmia Assay initiative) is a project driven by the Health and Environmental Science Institute (HESI), the FDA and the Safety Pharmacology Society. It aims to optimize the assessment of clinical potential of TdP and to replace the preclinical hERG current assay required under the ICH S7B safety pharmacology guideline by a specific combination of the above-mentioned methodologies, i.e. patch clamp and MEA, combined with in silico modelling.
As member of HESI, the NMI participated successfully in the CiPA Myocyte pilot study in 2014/2015 and as core site partner in a major international multi-site validation study in 2016/2017. The validation study confirmed the utility of hiPS cardiomyocytes on MEA based on electrophysiologic responses to 28 blinded drugs, with minimal influence from cell lines, test sites, and electrophysiological platforms.
For more information visit www.cipaproject.org
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Kraushaar U, Meyer T, Hess D, Gepstein L, L Mummery C, R Braam S, et al. Cardiac Safety Pharmacology: From Human ether-a-gogo Related Ggene Channel Block Towards Induced Pluripotent Stem Cell-based Disease Models. Expert Opinion on Drug Safety 2011 | Contact an author.
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