The FDA’s Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is designed to remove the over-reliance on hERG data to predict human clinical cardiac risk, with recent results suggesting that inclusion of additional cardiac ion channels and assays (e.g. peak and late Nav1.5, Cav1.2, dynamic hERG) improve risk predictions of in silico action potential models. The CiPA working groups currently use a mixture of manual and automated patch-clamp (APC) platform data, but future CiPA drug screening will likely rely on APC data.
Optical voltage imaging of human iPSC-derived cardiomyocytes was used to assess electrophysiological effects of compounds beyond hERG inhibition. Action potential waveform analysis revealed compound-specific and concentration-dependent changes, enabling mechanistic differentiation of multichannel activity and demonstrating a human-relevant approach for translational cardiac safety assessment.
The presence of sensory neuron markers, excitability properties consistent with sensory neurons, and evidence of nociceptor ion channels (using both RNASeq and electrophysiology) provides strong evidence that iCell Sensory Neurons have a robust sensory neuron phenotype suitable for supporting pain discovery programs.