(1356-A) Phenotypic Screening using hPSC Neurons on Multi-Electrode Array (MEA) with Novel Analysis Methodology combined with Genedata Screener
Monday, February 5, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: MEA provides high content multi-parametric data (>70 metrics) allowing phenotypic screening for multiple indications, including seizure liability. Seizure phenotypes vary depending on induction mechanism and require interpretation of multiple parameters to fully interrogate the phenotype. This breadth of data results in significant challenges interpreting the results to make meaningful decisions. Charles River, in collaboration with Genedata, have developed a customisation for Screener which integrates with the screening protocols at Charles River to automate and increase throughput of data analysis. Using this customisation, in our validated human tri-culture system (Glutamatergic and GABAergic neurons with astrocytes) of spontaneous neuronal firing, we describe the activity of a seizurogenic compound, Bicuculline, and assess the effect of known anti-epileptic drugs, Retigabine and Flupirtine. Without the customisation, manual analysis was limited to 5 metrics to describe compound activity due to data-handling constraints whereas the new customisation allows examination of all 73 metrics over 16 time points and uses a non-biased PCA analysis to find the most phenotypically relevant metrics. In addition, the customisation allows assessment of culture development and visualization of compound effects both over time and in concentration-response. This refined analysis pipeline enhances our ability to understand and communicate complex, translational MEA data which can be used to assess neurotoxicity, seizurogenic liability and disease-relevant phenotypic changes. Ultimately, this will aid in the development of novel therapeutics.