CiPA logoThe International Council on Harmonization (ICH) S7B and E14 regulatory guidelines were introduced in 2005 to evaluate the proarrhythmic liability of new drugs.
Base impedance, an indicator of cell viability, can be used to non-invasively identify structural and functional cardiotoxicity over a chronic time course.
We have developed a chronic cardiotoxicity assay using human hiPSC-derived cardiomyocytes, which has been validated with a number of cardiotoxicants. For example, doxorubicin, a member of the anthracycline family that is used to treat breast cancer, is associated with a number of cardiac side effects, which includes acute atrial and ventricular arrhythmias, chronic cardiomyopathy and congestive heart failure.
This chronic cardiotoxicity assay recapitulates doxorubicin’s cardiotoxic effect by producing a concentration-dependent decrease of base impedance that develops following a 24 hour exposure period.
Figure 1. Effects of Doxorubicin on hiPSC impedance.
CiPA logoThe International Council on Harmonization (ICH) S7B and E14 regulatory guidelines were introduced in 2005 to evaluate the proarrhythmic liability of new drugs.
In light of the FDA’s changing stance, the Volta assay emerges as a powerful, validated NAM capable of addressing the very safety concerns traditionally assessed in animal studies.