Development of a toxicological assay for prediction of drug-induced seizure in human iPS cell-derived neurons

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15577
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Tohoku University
• Principal Investigator: Odawara Aoi 東北大学, 材料科学高等研究所, JSPS特別研究員(PD) (80795287)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: ヒトiPS細胞由来ニューロン / 平面微小電極アレイ / 同期バースト発火 / 薬効評価 / 人工知能

Outline of Final Research Achievements

Functional evaluation assays using human induced pluripotent stem cell (hiPSC)-derived neurons are expected to predict the convulsion toxicity of new drugs. However, culture protocol on the micro-electrode array (MEA) in hiPSC-derived neurons and an evaluation index of MEA data are not well known. In this study, we investigated the difference of spontaneous firings and drug responses depending on the type of human iPS cell-derived neurons, cell density, medium conditions, and astrocyte co-culture conditions. It was found that the responsiveness differs depending on the culture conditions, and that one parameter is difficult to detect seizure-like toxicity. We also show that the synchronized burst firings (SBFs) detection method using AI, nonlinear time series analysis method, and frequency analysis method are effective as analysis method.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

ヒトiPS細胞由来ニューロンの微小電極アレイ（MEA）計測法を用いた薬剤性痙攣予測法は、国内外で製薬会社も含めた取り組みが行われており、本研究成果は、実用化を推進する成果であり、社会的意義は大きい。