CARDIOTOXICITY

PREDICTIVE TOXICOLOGY

Liver, heart, kidney and brain drug-induced toxicities currently account for more than 70% of drug attrition and drug withdrawal. Porsolt together with Fluofarma has developed a range of organ-specific cell-based assays to better predict the toxicity potential of drug candidates prior to in vivo studies.

CARDIOTOXICITY

Investigation of effects of new chemical entities (NCEs) on the extra-cellular field potential of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs)

> Comprehensive in vitro Proarrhythmia Assay (CiPA).

Cardiomyocytes together with the capabilities of MEA platform provide important predictive cardiac electrophysiology data, matching the needs of the pharmaceutical industry to assess drug liability early in the drug discovery process.

Calcium transient assay on hiPSC-CMs

Since calcium is the link between excitation and contraction of the cardiomyocytes, analyzing the Calcium transients provide an obvious and simple output.

Any arrhythmia / irregularity in the calcium transients, observed on this normally highly synchronous syncytial bed of cardiomyocytes, can provide useful indication of cardiotoxicity.

Calcium transient assay is performed in a miniaturized 384-well plate format, suitable for screening small to large series of compounds.

in vitro proarrhythmic risk assessment

While the hERG channel is still considered to be the main target for in vitro proarrhythmic risk assessment, a rapid and preliminary test of the L type calcium current (ICaL), the rapid component of the sodium current (INa) and the ionic currents responsible for maintaining resting membrane potential (the inward rectifier potassium current IK1) using the patch-clamp technique in transfected cells is recommended for drawing a more complete cardiac risk profile of a new drug.