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Development of innovative tauopathy therapeutic agents using catalytic antibodies

Research Project

Project/Area Number 18K06589
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
Research InstitutionSuzuka University of Medical Science

Principal Investigator

Taguchi Hiroaki  鈴鹿医療科学大学, 薬学部, 教授 (20549068)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords抗体酵素 / タウオパチー / タウタンパク質 / 抗体医薬 / ペプチド
Outline of Final Research Achievements

Tauopathy is a general term for neurodegenerative diseases in which a large amount of tau protein, which is a microtubule-associated protein, is stored in nerve cells, and includes Alzheimer's disease and the like. In this study, we designed and synthesized catalytic antibody-inducing reagents for generating a catalytic antibody that cleaves tau protein, which would be the causative molecule of tauopathy. We have successfully synthesized a catalytic antibody-inducing reagent by molecularly designing a catalytic antibody-inducing reagent containing the amino acid sequence that expresses tau protein aggregation and subsequent neurotoxicity, and by combining a solid-phase peptide synthesis method and a liquid phase method.

Academic Significance and Societal Importance of the Research Achievements

効果的な治療薬がないタウオパチーの治療薬の創製を目指し、タウタンパク質を分子標的とした抗体酵素を得る誘導体試薬の合成は、タウタンパク質を特異的に加水分解する抗体を作製することができる独自のアプローチであり、学術的評価は高い。また、これまで根本的治療薬がなかったタウオパチーの治療を大きく前進させることができる可能性がある。また、抗体酵素は既存の抗体医薬に比べ、投与量を大幅に減少させることができることから、抗体医薬がかかえる副作用や高額な医療費などの問題を解決することが期待されるため、社会的意義もあると考えている。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2022 2021 2020 2019

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Finding and characterizing a catalytic antibody light chain, H34, capable of degrading the PD-1 molecule2021

    • Author(s)
      Hifumi Emi、Taguchi Hiroaki、Nonaka Tamami、Harada Takunori、Uda Taizo
    • Journal Title

      RSC Chemical Biology

      Volume: 2 Issue: 1 Pages: 220-229

    • DOI

      10.1039/d0cb00155d

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new algorithm to convert a normal antibody into the corresponding catalytic antibody2020

    • Author(s)
      Emi Hifumi, Hiroaki Taguchi, Haruna Tsuda, Tetsuro Minagawa, Tamami Nonaka, and Taizo Uda
    • Journal Title

      Sci Adv.

      Volume: 6 Issue: 13 Pages: 6441-6441

    • DOI

      10.1126/sciadv.aay6441

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discovery of Antibody Light Chains Possessing Tau Protein-Hydrolyzing Activity2020

    • Author(s)
      Hiroaki Taguchi1, Yuki Kato, Taminao Ito, Emi Hifumi, and Taizo Uda
    • Journal Title

      Peptide science

      Volume: 56 Pages: 139-140

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of Physical Damage in the Intermediate Phase on the Progression of Amyloid β Fibrillization2019

    • Author(s)
      Ryu Tashiro, Hiroaki Taguchi, Kumi Hidaka, Masayuki Endo, Hiroshi Sugiyama
    • Journal Title

      Chem. Asian J.

      Volume: 14 Issue: 23 Pages: 4140-4145

    • DOI

      10.1002/asia.201901193

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discovery of Antibody Light Chains Capable of Hydrolyzing Tau Protein Using Fluorescence-Quenched Substrate2019

    • Author(s)
      Hiroaki Taguchi, Iida Yuki, Mao Oba, Yoshio Fujita, Emi Hifumi, Taizo Uda
    • Journal Title

      Peptide science 2018

      Volume: 55 Pages: 40-40

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] New technologies to introduce a catalytic function into antibodies: A unique human catalytic antibody light chain showing degradation of β‐amyloid molecule along with the peptidase activity2019

    • Author(s)
      Emi Hifumi, Hiroaki Taguchi, Eiichi Toorisaka, Taizo Uda
    • Journal Title

      FASEB BioAdvances

      Volume: 1 Issue: 2 Pages: 93-104

    • DOI

      10.1096/fba.1025

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of the minimal region of peptide derived from ADP-ribosylation factor1 (ARF1) that inhibits IgE-mediated mast cell activation2019

    • Author(s)
      Uchida Ryota、Egawa Tomonori、Fujita Yoshio、Furuta Kazuyuki、Taguchi Hiroaki、Tanaka Satoshi、Nishida Keigo
    • Journal Title

      Molecular Immunology

      Volume: 105 Pages: 32-37

    • DOI

      10.1016/j.molimm.2018.11.002

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Inhibition of amyloid-beta aggregation by catalytic light chain antibodies2022

    • Author(s)
      水谷百恵、一二三恵美、宇田泰三、田口博明
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] アミロイドβペプチドを加水分解する 抗体酵素の開発2021

    • Author(s)
      田口博明、一二三恵美、宇田泰三
    • Organizer
      第40回日本認知症学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Discovery of Antibody Light Chains Possessing Tau Protein-Hydrolyzing Activity2019

    • Author(s)
      田口 博明、伊藤 民直、加藤 佑規、一二三 恵美、宇田 泰三
    • Organizer
      第56回ペプチド討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] タウタンパク質を加水分解する抗体酵素の開発2019

    • Author(s)
      田口 博明、伊藤 民直、加藤 佑規、一二三 恵美、宇田 泰三
    • Organizer
      第38回日本認知症学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] タウタンパク質のリピート2部分を加水分解する抗体酵素の開発2019

    • Author(s)
      田口 博明、伊藤 民直、加藤 佑規、一二三 恵美、宇田 泰三
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Discovery of Antibody Light Chains Capable of Hydrolyzing Tau Protein Using Fluorescence-Quenched Substrate2019

    • Author(s)
      Hiroaki Taguchi, Iida Yuki, Mao Oba, Yoshio Fujita, Emi Hifumi, Taizo Uda
    • Organizer
      10th international peptide symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] アミロイドβ1-42プロトフィブリルの伸長のリアルタイム観測2019

    • Author(s)
      田代 竜、田口 博明、日高 久美、遠藤 政幸、杉山 弘
    • Organizer
      日本薬学会東海支部会
    • Related Report
      2018 Research-status Report
  • [Presentation] Observation of growing amyloid protofibrils 2D network with high speed AFM2019

    • Author(s)
      Ryu Tashiro, Hiroaki Taguchi, Kumi Hidaka, Masayuki Endo, Hiroshi Sugiyama
    • Organizer
      日本ケミカルバイオロジー学会第14回年会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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