Research on Dravet syndrome by using patient-derived iPS cells and a rat model

2017 Fiscal Year Final Research Report

• Project/Area Number: 26461552
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Jikei University School of Medicine
• Principal Investigator: HIGURASHI NORIMICHI 東京慈恵会医科大学, 医学部, 講師 (40568820)
• Research Collaborator: TAHARA Mayu 東京慈恵会医科大学, 医学部, 大学院生
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: てんかん / 病態 / 細胞治療 / iPS細胞 / モデルラット / MRI / 遺伝子

Outline of Final Research Achievements

Dravet syndrome (DS) is an infantile-onset intractable epilepsy, mainly caused by mutation in SCN1A gene. This research aims to elucidate novel pathomechanisms on DS and to achieve a transplantation therapy of GABAergic inhibitory precursors in the future. In the present study, 1) we developed a method to efficiently induce GABAergic neurons from human induced pluripotent stem cells (iPSCs). 2) We established mutation-repaired iPSCs from a patient-derived iPSCs by using a TALEN-based genome-editing technology. 3) Finally, to identify brain regions that is involved in the epilepsy pathogenesis in DS, we employed a manganese-enhanced magnetic resonance imaging technique, which may detect regions with increased neuronal activity. We identified several enhanced regions including hippocampus, thalamus, and some neocortical areas. Although further evaluations are necessary, this method will elucidate anatomical basis for epileptogenesis and target regions for cell therapy.

Free Research Field

医歯薬学