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Establishment of a Monitoring and Evaluation Platform for the Development of Disease-Modifying Drugs in Progressive Supranuclear Palsy

Research Project

Project/Area Number 21K15705
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52020:Neurology-related
Research InstitutionNational Institutes for Quantum Science and Technology

Principal Investigator

Hironobu Endo  国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 脳機能イメージング研究部, 主任研究員 (10894397)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords進行性核上性麻痺 / タウPET / タウオパチー / バイオマーカー
Outline of Research at the Start

進行性核上性麻痺(PSP)は、病状進展とともに脳内異常タウたんぱくが蓄積し、運動・認知機能障害を呈する不治の神経難病である。易発年齢が高齢のため、近年の人口高齢化に伴い罹患者数が増えており、根本治療薬の開発は喫緊の課題である。申請者が所属する量研機構では、PSPのタウ病変を生体内で可視化するタウPETリガンド[18F]PM-PBB3を開発した。この技術を用いたPSP鑑別診断法は確立されつつあるが、縦断的な症状進行評価や予後予測に対する指標は確立されていない。PSPにおけるタウたんぱく病変の縦断的な分布の変化と神経障害、症状との関連を検討し、治療法開発に向けたモニタリング評価基盤の確立を目指す。

Outline of Final Research Achievements

Progressive supranuclear palsy (PSP) is an incurable neurological disease caused by the accumulation of abnormal tau protein (tau lesions) in the brain, and the development of a fundamental therapeutic agent is an urgent issue. The National Institutes for Quantum Science and Technology, to which the applicant belongs, has developed the tau PET ligand [18F]PM-PBB3 to visualize tau lesions in PSP in vivo. Although differential diagnostic methods for PSP using this technology are being established, indices for longitudinal evaluation of symptom progression and prognosis prediction have not been established. In this study, we developed an objective measure of tau protein lesions in PSP and examined the association between longitudinal changes and clinical symptoms. This index will serve as a monitoring and evaluation basis for the development of treatment methods, and is expected to further promote the development of treatment methods in the future.

Academic Significance and Societal Importance of the Research Achievements

PSPにおけるタウ病変は、生前PSPにおいてどのように変化し、脳萎縮や神経症状へ影響しているのか不明である。本研究では、PSPのタウ病変を客観的な指標化し、経時的変化を評価することで、臨床症状との関連を明らかにした。また治療法開発の基盤となるモニタリング評価基盤の確立のため、画像解析のプラットフォームを整備した。本研究によりイメージングによるPSP縦断評価基盤が作成され、タウ病変を標的とした治療法開発が今後一層促進されることが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (4 results)

All 2023 2022 2021

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] A Machine Learning-Based Approach to Discrimination of Tauopathies Using [18F]PM-PBB3 PET Images2022

    • Author(s)
      Endo Hironobu、Tagai Kenji、Ono Maiko、Ikoma Yoko、Oyama Asaka、Matsuoka Kiwamu、Kokubo Naomi、Hirata Kosei et al.
    • Journal Title

      Movement Disorders

      Volume: 37 Issue: 11 Pages: 2236-2246

    • DOI

      10.1002/mds.29173

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Longitudinal PET assessments of tau pathologies in progressive supranuclear palsy with 18F-florzolotau (PM-PBB3/APN-1607)2023

    • Author(s)
      Hironobu Endo, Yuhei Takado, Kenji Tagai, et al.
    • Organizer
      Human Amyloid Imaging Conference 2023
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishment of diagnostic system for progressive supranuclear palsy using in vivo tau imaging2021

    • Author(s)
      遠藤 浩信
    • Organizer
      第62回日本神経学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] タウPETを用いた機械学習に基づく非アルツハイマー型認知症の自動診断法開発2021

    • Author(s)
      遠藤 浩信
    • Organizer
      第40回日本認知症学会学術集会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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