Neurotoxicological effects now rank second behind cardiovascular events as adverse events impeding the development and safety of new drug candidates. Accordingly, Metrion has developed assays that can be used to predict seizurogenic and neurotoxic compound activity in the peripheral and central nervous system using native neurons, and are now building similar assays with human stem-cell derived neurons. Both approaches provide a translational step for development of anticonvulsant compounds and safe and effective treatments for other central nervous system diseases.
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.