Prediction of Seizure Liability and Mechanism of Action Using Human iPSC-Derived Neuronal Cells and Astrocytes

Abstract

The global trend towards the abolition of animal testing and the enactment of the FDA Modernization Act 2.0 have led to heightened expectations for in vitro testing methods that extrapolate to in vivo. The microelectrode array (MEA) measurement method, which allows for non-invasive measurement of in vitro neural activity, is one such method. It serves as a toxicity assessment method based on functional indicators and is also under consideration for inclusion in the OECD's developmental neurotoxicity assessment. This presentation will introduce methods for predicting seizure liability using MEA measurements of human iPSC-derived central neurons and astrocytes, as well as approaches to extrapolate in vitro data to vivo. Subsequently, it will present methods for predicting the mechanism of action based on data from 100 compounds obtained from cortical neurons, dopaminergic neurons, and astrocytes. Additionally, it will introduce the field potential imaging using state-of-the-art CMOS-MEA and big data analysis, as well as discuss its advantages.