[Approach to drug efficacy and safety assessment based on functions of a human iPSC-derived neuronal network]

Development of an in vitro drug efficacy and safety assessment based on the function of the neural network is required in preclinical studies. A microelectrode array (MEA), which can simultaneously measure the electrical activity of a human induced pluripotent stem cell-derived neural network at multiple points, is an effective assay system. In this study, we focused on seizure liability and clarified the responsiveness to seizure-positive compounds depending on the excitatory and inhibitory balance (E/I balance) of each evaluation sample. In addition, it has been shown that multivariate analysis and AI analysis methods are effective for detecting toxicity and predicting drug mechanisms of action. The future challenge is to approach in vitro-to-in vivo extrapolation (IVIVE) for in vitro assessment. An assessment using brain organoids and low-frequency component analysis, in which enable comparison with in vivo ECoG are effective approaches to IVIVE. MEA can be applied to the central nervous system and the peripheral nervous system; therefore, MEA is also expected to become a highly useful assessment tool for peripheral neuropathy.