Exploring the Utility of iPSC-derived 3D Cortical Spheroids in the Detection of CNS Toxicity
Qin Wang,
Scientist, Drug Safety Research & Evaluation,
Takeda Pharmaceuticals, Inc.
Drug-induced Central Nervous System (CNS) toxicity is a common safety attrition for project failure during discovery and development phases due to low concordance rates between animal models and human, absence of clear biomarkers, and a lack of predictive assays. To address the challenge, we validated a high throughput human iPSC-derived 3D microBrain model with a diverse set of pharmaceuticals. We measured drug-induced changes in neuronal viability and Ca channel function. MicroBrain exposure and analyses were rooted in therapeutic exposure to predict clinical drug-induced seizures and/or neurodegeneration. We found that this high throughput model has very low false positive rate in the prediction of drug-induced neurotoxicity. This assay has the potential to be used as a predictive assay to detect neurotoxicity hazard identification in early drug discovery.
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