ヒトiPS細胞由来神経細胞を用いた微小電極アレイシステムによる痙攣・てんかん評価法について

抄録

In the drug development in pharmaceuticals, development of drugs may be discontinued due to the toxicity and clinical side effect, therefore, safety assessment is one of the important factors in drug development. Recently, pre-clinical studies are screening for compounds by the in vitro screening system using human iPS cell-derived cells which are expected to predictively of human clinical. Human iPS Cell Applied Safety Assessment Consortium (CSAHi). CSAHi focuses on hepato-, cardio-, and neuro-toxicities as important toxicity organs which are attributed to the causes of discontinuation of drug development. In neurotoxicity, seizure is an important finding because of high frequency expression in nonclinical. Multi-electrode array (MEA) systems have recently attracted attention as useful for evaluating seizure risk because they can non-invasively measure the electrophysiological activities of neural networks. We are evaluating the electrophysiological responses to several seizure compounds using MEA in cultured hiPSC-derived neurons. It is important to establish an analytical method to detecting seizure-like activities. We have focused the periodicity of synchronized burst firings as one of the effective analytical parameters for detecting seizure risk. We identify the parameter sets that separate the responses between positive and negative compounds using principal component analysis of 10 parameters. The principal component analysis using parameter set focused on periodicity is useful method to detect the seizure risk.