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Development of novel multi-target drugs for intractable amyloidoses

Research Project

Project/Area Number 15K15006
Research Category

Grant-in-Aid for Challenging Exploratory Research

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

Principal Investigator

Jono Hirofumi  熊本大学, 医学部附属病院, 准教授 (40515483)

Co-Investigator(Kenkyū-buntansha) 安東 由喜雄  熊本大学, 大学院生命科学研究部(医), 教授 (20253742)
有馬 英俊  熊本大学, 大学院生命科学研究部(薬), 教授 (50260964)
白木 伸明  東京工業大学, 生命理工学院, 准教授 (70448520)
Research Collaborator Butler James  
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords高機能性遺伝子キャリア / アミロイドーシス / 家族性アミロイドポリニューロパチー
Outline of Final Research Achievements

Intractable amyloidoses progress through 3 critical pathological processes, 1. Overproduction or mutation of amyloid precursor proteins, 2. Amyloid fibril formation caused by conformational change, 3. Tissue deposition of amyloid fibrils. However, as of this moment, no clinically effective therapy targeting each pathological process independently is available. In this research, we utilized characteristic features of polyamidoamine starburst dendrimer as a multifunctional material and developed novel multi-target drugs (GUG-β-CDE) for FAP effectively suppressing 3 pathological process in parallel.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Acknowledgement Compliant: 1 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] Alnylam Pharmaceuticals, Inc.(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Novel Antibody for the Treatment of Transthyretin Amyloidosis.2016

    • Author(s)
      Hosoi A, Su Y, Torikai M, Jono H, Ishikawa D, Soejima K, Higuchi H, Guo J, Ueda M, Suenaga G, Motokawa H, Ikeda T, Senju S, Nakashima T, Ando Y
    • Journal Title

      J Biol Chem

      Volume: 291 Pages: 25096-25105

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sources of variation of transthyretin in healthy subjects in East and Southeast Asia: Clinical and experimental evidence for the effect of alcohol on transthyretin metabolism.2016

    • Author(s)
      Jono H, Su Y, Obayashi K, Tanaka Y, Ishiguro A, Nishimura H, Shinriki S, Ueda M, Ikeda K, Yamagata K, Ichihara K, Ando Y; Scientific Committee for the Asia-Pacific Federation of Clinical Biochemistry.
    • Journal Title

      Clin Chim Acta

      Volume: 458 Pages: 240-5

    • DOI

      10.1016/j.cca.2016.04.011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long-term outcome of patients with hereditary transthyretin V30M amyloidosis with Polyneuropathy after liver transplantation2016

    • Author(s)
      Okumura K, Yamashita T, Masuda T, Misumi Y, Ueda A, Ueda M, Obayashi K, Jono H, Yamashita S, Inomata Y, Ando Y
    • Journal Title

      Amyloid

      Volume: 13 Pages: 1-7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term outcome of patients with hereditary transthyretin V30M amyloidosis with polyneuropathy after liver transplantation.2016

    • Author(s)
      Okumura K, Yamashita T, Masuda T, Misumi Y, Ueda A, Ueda M, Obayashi K, Jono H, Yamashita S, Inomata Y, Ando Y.
    • Journal Title

      Amyloid

      Volume: 23 Issue: 1 Pages: 39-45

    • DOI

      10.3109/13506129.2015.1123149

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis.2015

    • Author(s)
      Yanagisawa A, Ueda M, Sueyoshi T, Okada T, Fujimoto T, Ogi Y, Kitagawa K, Tasaki M, Misumi Y, Oshima T, Jono H, Obayashi K, Hirakawa K, Uchida H, Westermark P, Ando Y, Mizuta H.
    • Journal Title

      Mod Pathol

      Volume: 28 Issue: 2 Pages: 201-207

    • DOI

      10.1038/modpathol.2014.102

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of insulin amyloid fibril formation by cyclodextrins.2015

    • Author(s)
      Kitagawa K, Misumi Y, Ueda M, Hayashi Y, Tasaki M, Obayashi K, Yamashita T, Jono H, Arima H, Ando Y.
    • Journal Title

      Amyloid

      Volume: 22 Issue: 3 Pages: 181-186

    • DOI

      10.3109/13506129.2015.1064818

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 質量分析法が変える難治性アミロイドーシスの治療戦略2017

    • Author(s)
      城野博史、田崎雅義、安東由喜雄
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 家族性アミロイドポリニューロパチー患者由来iPS細胞を用いた病態解および創薬スクリーニングの有用性2016

    • Author(s)
      城野博史、竹下うらん、大内健太、成田泰子、磯野香織、大矢雄希、猪股裕紀洋、安東由喜雄
    • Organizer
      第56回日本臨床化学会年次学術集会
    • Place of Presentation
      熊本
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] アミロイドーシス根治を目指した革新的マルチターゲット型治療薬の創製2016

    • Author(s)
      城野博史
    • Organizer
      第4回TR推進合同フォーラム・ライフサイエンス技術交流会
    • Place of Presentation
      福岡
    • Year and Date
      2016-10-31
    • Related Report
      2016 Annual Research Report
  • [Presentation] Therapeutic effect of polyamidoamine dendrimer on transthyretin-related amyloidosis2016

    • Author(s)
      Jono H, Anno T, Hayashi Y, Motoyama K, Ueda M, Obayashi K, Arima H, Ando Y
    • Organizer
      XV International Symposium on Amyloidosis
    • Place of Presentation
      Uppsala, Sweden
    • Year and Date
      2016-07-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アミロイドーシス根治を目指した革新的マルチターゲット型治療薬の創製2015

    • Author(s)
      城野博史
    • Organizer
      第3回TR推進合同フォーラム
    • Place of Presentation
      福岡
    • Year and Date
      2015-08-31
    • Related Report
      2015 Research-status Report
  • [Presentation] Novel cyclodextrin-based therapeutic approaches for refractory Amyloidosis2015

    • Author(s)
      Jono H, Inoue M, Fujisawa K, Hayashi Y, Anno T, Motoyama K, Ando Y, Arima H
    • Organizer
      8th Asian Cyclodextrin Conference and 32nd Cyclodextrin Symposium
    • Place of Presentation
      Kumamoto
    • Year and Date
      2015-05-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Patent(Industrial Property Rights)] 新規なアミロイド線維生成抑制剤2016

    • Inventor(s)
      城野博史、有馬英俊、安東由喜雄、本山敬一、東大志
    • Industrial Property Rights Holder
      城野博史、有馬英俊、安東由喜雄、本山敬一、東大志
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-06-10
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規なアミロイド線維生成抑制剤2015

    • Inventor(s)
      城野博史、有馬英俊、安東由喜雄、本山敬一、東大志
    • Industrial Property Rights Holder
      城野博史、有馬英俊、安東由喜雄、本山敬一、東大志
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-117150
    • Filing Date
      2015-06-10
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-02-16  

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