Identification of therapeutic targets and drug discovery research for Dravet syndrome using iPSCs model

2017 Fiscal Year Final Research Report

• Project/Area Number: 26860833
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Fukuoka University
• Principal Investigator: Tanaka Yasuyoshi 福岡大学, てんかん分子病態研究所, ポスト・ドクター (50714466)
• Research Collaborator: SASAGURI Yukari
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: Dravet症候群 / SCN1A / iPS細胞 / TALEN / ゲノム編集 / 興奮性神経 / 抑制性神経

Outline of Final Research Achievements

In order to contribute to deciphering the pathogenic mechanisms and facilitating drug discovery for Darvet syndrome (DS), we established 1) patient-derived iPSCs, 2) generated an isogenic control cell line derived from DS patient iPSCs by genome editing using TALEN method, and 3) investigated the functional differences in neuronal cells between control and DS cells via functional analysis of action potential measurement.
In this study, we generated iPSC lines derived from three DS patients. To establish isogenic control cells, we generated a genome-edited control cell line from one of the DS iPSC lines by substituting the point mutation with the wild-type residue using TALEN. This artificial control iPSC line will be a powerful tool for research into the pathology of DS. We measured action potential in iPSC-derived excitatory neurons by use of a microelectrode array system. The results of this study can be applied to research for drug discovery and development against DS.

Free Research Field

医歯薬学