Suzuki Ikuro
Department of Electronics, Graduate School of Engineering, Tohoku Institute of Technology.
Nihon Yakurigaku Zasshi. 2020;155(5):289-294. doi: 10.1254/fpj.20031.
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.
临床前研究需要基于神经网络功能开发体外药物疗效和安全性评估方法。微电极阵列（MEA）能够同时多点测量人诱导多能干细胞衍生神经网络的电活动，是一种有效的检测系统。在本研究中，我们关注癫痫易感性，并根据每个评估样本的兴奋与抑制平衡（E/I平衡）阐明了对癫痫阳性化合物的反应性。此外，多变量分析和人工智能分析方法已被证明对检测毒性和预测药物作用机制有效。未来的挑战是在体外评估中实现体外到体内外推（IVIVE）。使用脑类器官和低频成分分析进行评估，能够与体内脑电图（ECoG）进行比较，是实现IVIVE的有效方法。MEA可应用于中枢神经系统和周围神经系统；因此，MEA也有望成为用于周围神经病变的非常有用的评估工具。
