Comparative study for the IMI2-NeuroDeRisk project on microelectrode arrays to derisk drug-induced seizure liability

Jin Zhai, Martin Traebert, Kurt Zimmermann, Annie Delaunois, Leandro Royer, Giorgia Salvagiotto, Coby Carlson, and Armando Lagrutta

Journal of Pharmacological and Toxicological Methods, 25 July 2023


In an effort to improve preclinical drug development, researchers investigate the use of multielectrode array assays to assess neurotoxicity in vitro.  

During preclinical drug development, identifying compounds that may lead to seizure activity is critical for patient safety and to avoid costly withdrawals before registration or filing. In conjunction with the European Innovative Medicines Initiative (IMI2) NeuroDeRisk consortium—a group that aims to “improve the predictivity of preclinical models for derisking seizure inducing liabilities”—the authors in this study evaluate the use of multielectrode array (MEA) assays as an alternative to animal models to de-risk drug development and predict drug-induced epileptic effects. 

Using two cell models, primary rat cortical neurons and human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons co-cultured with hiPSC-derived astrocytes, the team used Axion’s noninvasive, label-free Maestro Pro MEA to assess the neurotoxicity of various compounds and create a novel "hyperexcitability index" incorporating multiple parameters. Overall, the authors suggest that hiPSC-derived neurons are “equivalent or even more sensitive than rat cortical neurons in detecting drug-induced seizurogenic activity,” and that, “Compared to more conventional measurements of evoked activity in hippocampal slices, these plate-based models provide higher throughput and the potential to study subacute responses.”