Use of new approach methodologies (NAMs) in epilepsy research and seizure risk assessment

Seizures are the hallmark of treatment-resistant epilepsy and are also a frequent adverse event in drug safety testing. Here we present a critical evaluation of new approach methodologies (NAMs) in epilepsy research and seizure liability. Specifically, recent data have shown that seizure can be profiled using an in vitro seizure liability assay (iSLA) comprising a microelectrode array (MEA) of human induced pluripotent stem cell (iPSC) neurons coupled with a human ion channel panel. Adverse outcome pathways (AOPs) also offer a powerful NAM framework to map how key events can lead to an adverse outcome such as seizure. These NAMs offers an innovative approach to antiseizure medication research as well as to seizure risk testing in drug discovery and development.