01620nas a2200349   4500000000100000000000100001008004100002260001500043653000800058653000800066653000900074653002100083653001900104653001600123653001300139653001800152653001700170653001200187100002000199700001500219700002200234700002300256700001900279700002400298700002200322700002400344245009400368300001100462490000700473520077600480022001401256       2025                            d  c2025-12-0310aCNS10aMEA10aNAMs10aDrug development10aDrug Discovery10adrug safety10aepilepsy10ahiPSC neurons10aion channels10aseizure1 aRuth A. Roberts1 aMamta Behl1 aHelena T. Hogberg1 aEduardo Dunayevich1 aMichael Morton1 aKimberly L. Rockley1 aAbigail L. Walker1 aJennifer B. Pierson00aUse of new approach methodologies (NAMs) in epilepsy research and seizure risk assessment  a1045690 v313 aSeizures 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.  a1878-5832