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Research on PCDH19 female epilepsy by using patient-derived iPS cells and a rat model

Research Project

Project/Area Number 24791095
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionJikei University School of Medicine (2013-2014)
Fukuoka University (2012)

Principal Investigator

HIGURASHI Norimichi  東京慈恵会医科大学, 医学部, 助教 (40568820)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsてんかん / 女性 / 遺伝子 / 疾患モデル動物 / 免疫 / 血液脳関門 / 接着分子 / 小児 / iPS細胞 / 脳血液関門
Outline of Final Research Achievements

To elucidate the pathogenic mechanisms and effective treatments of PCDH19 female epilepsy, we established 1) patient-derived iPS cells and 2) a model rat, and 3) further investigated the clinical aspects of newly identified patients. 1) We compared iPS cell-derived neurons among a normal control cell line, paternal X (mutated PCDH19)-active patient cell lines, and maternal X (wild type PCDH19)-active patient cell lines focusing on their morphology and PCDH19 expression. However, no significant pathogenic alteration was detected. 2) A Pcdh19-knockout rat was successfully established by using the TALEN technology and will be used for our future research. 3) We newly identified more than 20 Japanese patients and deepened our understanding of the clinical aspects of PCDH19 female epilepsy, specifically initial seizure characteristics, an excellent efficacy of corticosteroids for seizure clusters, and a possible involvement of immune processes in the pathogenic mechanisms.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (31 results)

All 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) (of which Invited: 10 results) Book (5 results)

  • [Journal Article] Immediate suppression of seizure clusters by corticosteroids in PCDH19 female epilepsy.2015

    • Author(s)
      Higurashi N, Takahashi Y, Kashimada A, Sugawara Y, Sakuma H, Tomonoh Y, Inoue T, Hoshina M, Satomi R, Ohfu M, Itomi K, Takano K, Kirino T, Hirose S.
    • Journal Title

      Seizure

      Volume: 27 Pages: 1-5

    • DOI

      10.1016/j.seizure.2015.02.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Clinical utility of neuronal cells directly converted from fibroblasts of patients for neuropsychiatric disorders: studies of lysosomal storage diseases and channelopathy.2015

    • Author(s)
      Kano S, Yuan M, Cardarelli RA, Maegawa G, Higurashi N, et al.
    • Journal Title

      Currrent Molecular Medicine

      Volume: 15 Issue: 2 Pages: 138-145

    • DOI

      10.2174/1566524015666150303110300

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 女性に発症するPCDH19関連てんかんの本邦例における臨床的特徴2013

    • Author(s)
      日暮憲道、他
    • Journal Title

      てんかん治療研究財団研究年報

      Volume: 24 Pages: 79-86

    • Related Report
      2013 Research-status Report
  • [Journal Article] The effect of SCN1A mutations on patient-derived GABAergic neurons: what are the implications for future Dravet syndrome therapeutics?2013

    • Author(s)
      Higurashi N, Okano H, Hirose S.
    • Journal Title

      Future Neurol

      Volume: 8 Issue: 5 Pages: 487-489

    • DOI

      10.2217/fnl.13.34

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Current Trends in Dravet syndrome Research.2013

    • Author(s)
      Higurashi N, Uchida T, Hirose S, Okano H.
    • Journal Title

      J Neurol Neurophysiol.

      Volume: 4 Issue: 03 Pages: 152-152

    • DOI

      10.4172/2155-9562.1000152

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] PCDH19-related female-limited epilepsy: further details regarding early clinical features and therapeutic efficacy.2013

    • Author(s)
      Higurashi N, Nakamura M, Sugai M, Ohfu M, Sakauchi M, Sugawara Y, Nakamura K, Kato M, Usui D, Mogami Y, Fujiwara Y, Ito T, Ikeda H, Imai K, Takahashi Y, Nukui M, Inoue T, Okazaki S, Kirino T, Tomonoh Y, Inoue T, Takano K, Shimakawa S, Hirose S.
    • Journal Title

      Epilepsy Res

      Volume: 106 Issue: 1-2 Pages: 191-199

    • DOI

      10.1016/j.eplepsyres.2013.04.005

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A human Dravet syndrome model from patient induced pluripotent stem cells.2013

    • Author(s)
      Higurashi N, Uchida T, Lossin C, Misumi Y, Okada Y, Akamatsu W, Imaizumi Y, Zhang B, Nabeshima K, Mori MX, Katsurabayashi S, Shirasaka Y, Okano H, Hirose S.
    • Journal Title

      Mol Brain

      Volume: 6 Issue: 1 Pages: 19-19

    • DOI

      10.1186/1756-6606-6-19

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Inflammatory aspects of PCDH19-related epilepsy.2014

    • Author(s)
      Higurashi N, et al.
    • Organizer
      第48回日本てんかん学会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] A Powerful Treatment Option for PCDH19-related Epilepsy.2014

    • Author(s)
      Higurashi N, Hirose S
    • Organizer
      PCDH19 Pediatric Epilepsy Professional and Family Symposium
    • Place of Presentation
      サンフランシスコ(米国)
    • Year and Date
      2014-09-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Dravet syndrome research using patient-derived induced pluripotent stem cells—Present findings and future directions.2014

    • Author(s)
      Higurashi N, Hirose S
    • Organizer
      Korea Epilepsy Congress (KEC 2014)
    • Place of Presentation
      ソウル(韓国)
    • Year and Date
      2014-06-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] シンポジウム:iPS細胞を用いた小児神経疾患の病態解明への期待とその問題点 ②てんかんの病態研究とその問題点2014

    • Author(s)
      日暮憲道
    • Organizer
      第56回日本小児神経学会総会
    • Place of Presentation
      浜松
    • Year and Date
      2014-05-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] High prevalence of autoantibodies to N-methyl-D-aspartate receptor and the efficacy of glucocorticoids in PCDH19-related female-limited epilepsy.2014

    • Author(s)
      Higurashi N, et al.
    • Organizer
      13th International Child Neurology Congress
    • Place of Presentation
      イグアス市(ブラジル)
    • Year and Date
      2014-05-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Potentials of induced pluripotent stem cell-derived neurons in future drug discovery for Dravet syndrome.2014

    • Author(s)
      Higurashi N, et al.
    • Organizer
      The 7th Takeda Science Foundation Symposium on PharmaSciences
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] Modeling Dravet syndrome using induced pluripotent stem cells2013

    • Author(s)
      Higurashi N., et al.
    • Organizer
      Pediatric Academic Societies Annual Meeting 2013
    • Place of Presentation
      米国 ワシントンDC
    • Related Report
      2012 Research-status Report
  • [Presentation] A new research platform for Dravet syndrome using patient-derived induced pluripotent stem cells2013

    • Author(s)
      Higurashi N., et al.
    • Organizer
      XII Workshop on Neurobiology of Epilepsy (WONOEP 2013)
    • Place of Presentation
      カナダ ケベック州ローレンシャン
    • Related Report
      2012 Research-status Report
  • [Presentation] PCDH19関連てんかんにおける発症初期の臨床的特徴と治療効果の検討2013

    • Author(s)
      日暮憲道、他
    • Organizer
      第55回日本小児神経学会学術総会
    • Place of Presentation
      大分市
    • Related Report
      2012 Research-status Report
  • [Presentation] 患者由来iPS細胞によるDravet症候群モデルの確立と分化GABA性神経細胞における機能低下2013

    • Author(s)
      日暮憲道、他
    • Organizer
      第47回日本てんかん学会
    • Place of Presentation
      北九州市
    • Related Report
      2012 Research-status Report
  • [Presentation] Dravet Syndrome or EFMR, What Is The Difference? – Can You Tell The Difference?2012

    • Author(s)
      Higurashi N., et al.
    • Organizer
      International Child Neurology Congress & 11th Asian & Oceanian Congress of Child Neurology
    • Place of Presentation
      オーストラリア ブリスベン
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Challenges in The Establishment of A Dravet Syndrome Model Using Patient-Derived iPS Cells.2012

    • Author(s)
      Higurashi N., et al.
    • Organizer
      Korean Epilepsy Congress 2012
    • Place of Presentation
      大韓民国 仁川
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Research on clinical aspects of PCDH19-related epilepsy and induced pluripotent stem cells from a patient with Dravet syndrome: Present findings and future directions.

    • Author(s)
      Higurashi N, et al.
    • Organizer
      7th IGAKUKEN International Symposium on “Fever, Inflammation, and Epilepsy”
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Early clinical features and treatment efficacy of antiepileptic drugs in Japanese patients with PCDH19-related epilepsy.

    • Author(s)
      Higurashi N, et al.
    • Organizer
      2nd Edition of World Conference on PCDH19
    • Place of Presentation
      ローマ(イタリア)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Dravet症候群とPCDH19関連てんかん―診断・鑑別のポイントと発症病態.

    • Author(s)
      日暮憲道
    • Organizer
      第47回日本てんかん学会
    • Place of Presentation
      北九州
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Modeling Dravet syndrome with patient-derived induced pluripotent stem cells and functional vulnerabilities in differentiated GABAergic neurons.

    • Author(s)
      Higurashi N, et al.
    • Organizer
      第47回日本てんかん学会
    • Place of Presentation
      北九州
    • Related Report
      2013 Research-status Report
  • [Presentation] PCDH19関連てんかんにおける発症初期の臨床的特徴と治療効果の検討

    • Author(s)
      日暮憲道、他
    • Organizer
      第55回日本小児神経学会総会
    • Place of Presentation
      大分
    • Related Report
      2013 Research-status Report
  • [Presentation] A new research platform for Dravet syndrome using patient-derived induced pluripotent stem cells

    • Author(s)
      Higurashi N, et al.
    • Organizer
      XII. Workshop on Neurobiology of the Epilepsy (WONOEP 2013)
    • Place of Presentation
      ケベック(カナダ)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Modeling Dravet Syndrome Using Induced Pluripotent Stem Cells.

    • Author(s)
      Higurashi N, et al.
    • Organizer
      Pediatric Academic Societies Annual Meeting (PAS 2013)
    • Place of Presentation
      ワシントンDC(米国)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 遺伝子医学MOOK 27号 iPS細胞を用いた難病研究-臨床病態解明と創薬に向けた研究の最新知見2015

    • Author(s)
      4.日暮憲道, 廣瀬伸一
    • Total Pages
      228
    • Publisher
      メディカル ドゥ
    • Related Report
      2014 Annual Research Report
  • [Book] 症例から学ぶ 戦略的てんかん診断・治療2014

    • Author(s)
      日暮憲道,井原由紀子,廣瀬伸一
    • Total Pages
      242
    • Publisher
      南山堂
    • Related Report
      2014 Annual Research Report
  • [Book] 日本臨牀別冊 神経症候群VI2014

    • Author(s)
      日暮憲道, 廣瀬伸一
    • Total Pages
      1000
    • Publisher
      日本臨牀社
    • Related Report
      2014 Annual Research Report
  • [Book] 稀少難治てんかん診療マニュアル―疾患の特徴と診断のポイント2013

    • Author(s)
      日暮憲道、他
    • Total Pages
      170
    • Publisher
      診断と治療社
    • Related Report
      2013 Research-status Report
  • [Book] 子どものけいれん・てんかん 見つけ方・見分け方から治療戦略へ2013

    • Author(s)
      日暮憲道、他
    • Total Pages
      268
    • Publisher
      中山書店
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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