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Amino acid transporter-based drug development for cerebral creatine deficiency syndrome

Research Project

Project/Area Number 16K15153
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionTohoku University

Principal Investigator

Terasaki Tetsuya  東北大学, 薬学研究科, 教授 (60155463)

Co-Investigator(Kenkyū-buntansha) 立川 正憲  東北大学, 薬学研究科, 准教授 (00401810)
吉田 将人  東北大学, 薬学研究科, 助教 (80511906)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords血液脳関門 / クレアチントランスポーター / クレアチン脳欠乏症 / 脳クレアチン欠乏症 / 薬学 / 脳・神経 / 生体機能利用
Outline of Final Research Achievements

The purpose of the present study was to establish the basis of creatine prodrug therapy for cerebral creatine deficiency with creatine transporter (CRT/SLC6A8) defect. Protein expression of transporters as the potent brain drug delivery pathways was clarified in developing rat blood-brain barrier based on quantitative targeted absolute proteomics. The patient-derived fibroblasts exhibited the cellular transport of the chemically synthesized creatine prodrug followed by the creatine generation.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Cell-type-specific spatiotemporal expression of creatine biosynthetic enzyme S-adenosylmethionine: guanidinoacetate N-methyltransferase in developing mouse brain2018

    • Author(s)
      Tachikawa M, Watanabe M, Fukaya M, Sakai K, Terasaki T, Hosoya K.
    • Journal Title

      Neurochem Res

      Volume: 43 Issue: 2 Pages: 500-510

    • DOI

      10.1007/s11064-017-2446-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Astrocytic γ-aminobutyric acid (GABA) transporters mediate guanidinoacetate transport in rat brain2018

    • Author(s)
      Tachikawa Masanori、Yashiki Ayane、Akanuma Shin-ichi、Matsukawa Haruka、Ide Soichiro、Minami Masabumi、Hosoya Ken-ichi
    • Journal Title

      Neurochem Int.

      Volume: 113 Pages: 1-7

    • DOI

      10.1016/j.neuint.2017.11.013

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 中枢薬剤学-Connecting the dots2018

    • Author(s)
      立川正憲
    • Organizer
      日本薬剤学会第32年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] クレアチン脳欠乏症治療を指向したカチオン性アミノ酸トランスポーターを輸送経路とするクレアチンプロドラッグの開発2017

    • Author(s)
      太田悠介、立川正憲、吉田将人、土井隆行、和田敬仁、寺崎 哲也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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