Epilepsy mechanism investigation and therapy development

• Project/Area Number: 25253073
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Yamakawa Kazuhiro 国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (30241235)
• Research Collaborator: SUZUKI Toshimitsu 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員
• Project Period (FY): 2013-05-31 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000); Fiscal Year 2017: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2016: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2014: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2013: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
• Keywords: てんかん / 遺伝子 / 若年ミオクロニーてんかん / 原因遺伝子 / 疾患動物モデル / マウスモデル / 治療 / JME / EFHC1 / 上衣細胞 / TRPM2

Outline of Final Research Achievements

Juvenile myoclonic epilepsy (JME) is the most frequent epilepsy. In this study, we identified ICK (intestinal cell kinase) as the gene responsible for JME, the disease mutations interfere neuronal migration, and Ick knockout mouse showed an increased siesure susceptibility to isoflirane（Bailey et al, New Eng J Med 378:1018-28, 2018). Similarly to the EFHC1 that we previously reported as a JME gene, ICK also play roles in microtubule regulation and neural cell migration suggesting an overlapping pathomechanism for JME.

Research Products

• [Int'l Joint Research] UCLA(米国)
• [Int'l Joint Research] University of Liege(Belgium)
• [Int'l Joint Research] UCLA(米国)
• [Int'l Joint Research] University of Liege(Belgium)
• [Journal Article] Variant Intestinal-Cell Kinase in Juvenile Myoclonic Epilepsy (2018)
  • Author(s): Bailey Julia N.、de Nijs Laurence、Bai Dongsheng、Suzuki Toshimitsu、Miyamoto Hiroyuki、Yamakawa Kazuhiro、Lakaye Bernard、Delgado-Escueta Antonio V. et al.
  • Journal Title: New England Journal of Medicine Volume: 378 Issue: 11 Pages: 1018-1028
  • DOI: 10.1056/nejmoa1700175
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] EFHC1 variants in Juvenile Myoclonic Epilepsy: Reanalysis according to NHGRI and ACMG Guidelines for assigning disease causality (2016)
  • Author(s): Bailey JN, Patterson C, de Nijs L, Duron RM, Nguyen VH, Tanaka M, Medina MT, Jara-Prado A, Martinez-Juarez IE, Ochoa A, Molina Y, Suzuki T, Alonso ME, Wight JE, Lin YC, Guilhoto L, Targas Yacubian EM, Machado-Salas J, Daga A, Yamakawa K, Grisar TM, Lakaye B, Delgado-Escueta AV.
  • Journal Title: Genetics in Medicine Volume: 19 Issue: 2 Pages: 144-156
  • DOI: 10.1038/gim.2016.86
  • Peer Reviewed / Int'l Joint Research
• [Remarks] てんかん原因遺伝子ICKの発見 －若年ミオクロニーてんかんの共通発症メカニズムを提示－
  • URL: http://www.riken.jp/pr/press/2018/20180315_1/
• [Remarks] 理化学研究所 脳科学総合研究センター 神経遺伝研究チーム
  • URL: http://www.brain.riken.jp/labs/ngs/indexj.html
• [Remarks] 独立行政法人理化学研究所 脳科学総合研究センター 神経遺伝研究チーム
  • URL: http://www.brain.riken.jp/labs/ngs/indexj.html