Development of molecular therapy for epilepsy using knock-in rats and artificial patient iPS cells with next generation methodologies

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H02548
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Fukuoka University
• Principal Investigator: Hirose shinichi 福岡大学, 医学部, 教授 (60248515)
• Research Collaborator: Inoue Ryuji ; Misumi Yoshio ; Katsurabayashi Shutaro ; Deshimaru Masanobu ; Koyama Susumu
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: てんかん / 遺伝子改変動物 / iPS細胞 / 分子病態 / 創薬

Outline of Final Research Achievements

Genetic abnormalities including some in two novel epilepsy genes have been identified in epilepsy phenotypes using the next generation sequence. The molecular pathogeneses of the epilepsy phenotypes have been also investigated with the genetic information available. Two strains of rats bearing genetic mutations identified in human epilepsy have been genetically engineered. Similarly, several strains of genetically engineered mice have been generated. The molecular pathomechanisms of epilepsies have been investigated in vivo with the animals. Artificial patient iPS cells harboring a mutation causing Dravet syndrome have been successfully generated. With these cells, the underlying molecular pathomechanisms of Dravet syndrome have been uncovered. With these genetically engineered animals and iPS cells, the development of novel therapies based upon the molecular pathogeneses of epilepsies have been initiated and several candidate compounds haven been found.

Free Research Field

神経内科

Academic Significance and Societal Importance of the Research Achievements

多様性に富むてんかんを正しく分類し診断することができ、より適切な治療が可能となり、遺伝相談への対応もより正確になった。今後、抗てんかん薬を病態に基づき開発可能で、副作用の少ない、より効果的な新薬が期待できる。また、てんかんの発症における年齢依存性の解明などを通じ、遺伝子の時限発現と脳の機能発達といった脳の生物学的理解が深まると期待される。以上から本研究の成果は、いまだ副作用の多い抗てんかん薬に頼らざるを得ない全世界1000万人以上と目される患者さんの健康福祉に貢献すると思われる。