Attrition due to neurotoxicity is a significant problem in drug discovery. Part of the problem lies in the fact that there aren’t any effective preclinical human neurotoxicity models on the market yet. Certain ion channel and receptor activity assays can predict some seizure potential, but they may not pick up reactions that are incited by multiple targets. This is a gap we have been trying to fill by developing eCiphr®Neuro, an MEA-based assay that measures neuronal electrophysiological response. The assay has been successful using rat cortical neurons, but with the goal of providing an assay that is more physiologically relevant to the human condition, we partnered with PhoenixSongs Biologicals to explore the utility of human neural stem cells (NSCs).
After treatment with a variety of GABAA antagonists at a range of predetermined time points, the cultures were monitored using the Axion BioSystems Maestro microelectrode array instrument. The NSC-derived cultures, which contain both neurons and astrocytes, showed patterns of change similar to rat cortical neurons. Further work is required and underway to improve the culturing process, as it currently takes about eight weeks to differentiate and mature the neurons, but the results indicate that development of an in vitro assay that predicts human neurotoxicity is both possible and, more importantly, practical.
Cyprotex presented this research as a poster presentation with PhoenixSongs Biologicals at SOT ToxExpo 2016.