An Integrated Approach for Early In Vitro Seizure Prediction Utilizing Human Derived Induced Pluripotent Stem Cells and Human Ion Channel Assays (S04-5)

Advances in stem cell biology coupled with an increased understanding of the role of ion channels in seizure offer an opportunity for a new paradigm in screening. We assessed the response of differentiated human induced pluripotent stem cell (hiPSC) neurones to 16 pro-seizurogenic compounds by microelectrode array (MEA). These compounds caused characteristic changes to electrical activity in key parameters indicative of seizure such as network burst frequency. Alongside the hiPSC/MEA approach, the same 16 seizurogenic compounds were screened against a panel of 15 ion channels with strong links to seizure using automated electrophysiology. We found that 15/16 compounds demonstrated at least one “hit” against the seizure panel and 9/16 compounds inhibited two or more ion channels. These studies highlight the potential utility of an integrated in vitro approach for early seizure prediction to provide mechanistic information and to support optimal drug design in early development, saving time and resources.