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Establishing Methods to Optimize the Treatment of Central Nervous System Inflammatory Diseases Using Genetic, Immunological, and Serological Markers

Research Project

Project/Area Number 22K07351
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionKyushu University

Principal Investigator

Watanabe Mitsuru  九州大学, 大学病院, 助教 (30748009)

Co-Investigator(Kenkyū-buntansha) 松下 拓也  高知大学, 教育研究部医療学系臨床医学部門, 教授 (00533001)
吉良 潤一  国際医療福祉大学, 医学研究科, 教授 (40183305)
磯部 紀子  九州大学, 医学研究院, 教授 (60452752)
Maimaitijiang Guzailiayi  国際医療福祉大学, トランスレーショナルニューロサイエンスリサーチセンター, 特任助教 (60887107)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords多発性硬化症 / 視神経脊髄炎スペクトラム障害 / 予後不良因子 / 環境要因 / 遺伝的要因 / 治療 / 環境因子 / 遺伝的因子 / 免疫細胞 / バイオマーカー / 治療選択
Outline of Research at the Start

中枢神経系の炎症性疾患である多発性硬化症および視神経脊髄炎スペクトラム障害は、いずれも適切な治療を行わないと将来身体機能障害や認知機能障害を来たす疾患である。近年様々な薬剤が使用できるようになってきているが、患者ごとに経過や治療反応性が異なるとともに、最適な治療薬を選択する指標は存在しない。そこで本研究では、患者の遺伝学的・免疫学的背景、疾患の活動性のバイオマーカー指標を総合的に評価し、どの治療薬を選択することが最適かを患者ごとに判断できるようになることを目的とする。これにより患者の長期予後を改善させ、過度な治療による不要なリスクを避け、さらには医療経済への負担も軽減させることが期待される。

Outline of Final Research Achievements

Using data from the nationwide survey on multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) conducted in 2018, we clarified that, in patients with MS, disease disability was independently influenced by age at onset, disease duration, progression to secondary progressive MS, smoking history, relapses within the first two years of disease onset, the presence of nine or more brain lesions, and spinal cord lesions. In patients with NMOSD, age at onset, disease duration, relapses within the first two years, and longitudinally extensive spinal cord lesions were found to be influential factors. Furthermore, using data from the Japan MS/NMOSD Biobank, we demonstrated that the MHC and CCR6 loci were associated with disease susceptibility, and that copy number variations in the chromosome 21q in CD4+ T cells conferred an increased risk for NMOSD.

Academic Significance and Societal Importance of the Research Achievements

日本人MS患者やNMOSD患者の疾患障害度に影響するリスク因子を明らかにした。MSの環境要因としては喫煙が挙がってきたことから、禁煙を指導することが障害進行予防にも有用であることが示唆された。
その他、NMOSDの発症の遺伝学的リスク関連領域を見出すとともに、CD4+T細胞の21番染色体長腕領域のコピー数変異がNMOSDのリスクになることを示した。このことからNMOSDという疾患の新たな病態機序の解明につながると期待される。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (17 results)

All 2025 2024 2023 2022

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder2025

    • Author(s)
      Yata Tomohiro、Sato Go、Ogawa Kotaro、Naito Tatsuhiko、Sonehara Kyuto、et al.
    • Journal Title

      Cell Genomics

      Volume: 5 Issue: 3 Pages: 100776-100776

    • DOI

      10.1016/j.xgen.2025.100776

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blood Exosome Connexins and Small RNAs Related to Demyelinating Disease Activity2025

    • Author(s)
      Maimaitijiang G, Kira J, Nakamura Y, Watanabe M, Takase EO, Nagata S, Sakoda A, Zhang X, Masaki K, Yamasaki R, Isobe N, Yamaguchi H, Imamura T.
    • Journal Title

      Annals of Clinical and Translational Neurology

      Volume: 12 Issue: 3 Pages: 538-555

    • DOI

      10.1002/acn3.52307

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prevalence of, and disability due to, multiple sclerosis and neuromyelitis optica spectrum disorder in Japan by the fifth nationwide survey.2024

    • Author(s)
      Watanabe M, Isobe N, Niino M, Nakashima I, Matsushita T, Sakai Y, Nakahara J, Kawachi I, Ochi H, Nakatsuji Y, Nakamura Y, Nakamura K, Sakata K, Matsui M, Kuwabara S, Kira J
    • Journal Title

      Neurology

      Volume: 103 Issue: 10

    • DOI

      10.1212/wnl.0000000000209992

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Efficacy of Eculizumab in the Acute Phase of Neuromyelitis Optica Spectrum Disorder: A Case Series Study2024

    • Author(s)
      Watanabe Mitsuru、Masaki Katsuhisa、Tanaka Eizo、Matsushita Takuya、Isobe Noriko
    • Journal Title

      Cureus

      Volume: 16

    • DOI

      10.7759/cureus.73205

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model.2024

    • Author(s)
      Takase EO, Yamasaki R, Nagata S, Watanabe M, Masaki K, Yamaguchi H, Kira J, Takeuchi H, Noriko Isobe.
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 10877-10877

    • DOI

      10.1038/s41598-024-61508-2

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of smoking on disease activity in multiple sclerosis patients treated with dimethyl fumarate or fingolimod2023

    • Author(s)
      Tanaka E, Watanabe M, Fukumoto S, Masaki K, Yamasaki R, Matsushita T, Isobe N
    • Journal Title

      Mult Scler Relat Disord

      Volume: - Pages: 104513-104513

    • DOI

      10.1016/j.msard.2023.104513

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Efficacy of Eculizumab in Acute Phase of Neuromyelitis Optica Spectrum Disorders: A Case Series Study2024

    • Author(s)
      Mitsuru Watanabe, Katsuhisa Masaki, Eizo Tanaka, Takuya Matsushita, Noriko Isobe
    • Organizer
      第65回日本神経学会学術大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 神経・筋疾患における補体標的治療2024

    • Author(s)
      渡邉 充
    • Organizer
      第60回日本補体学会学術集会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] Application of B cell therapy in MS & NMOSD2024

    • Author(s)
      Mitsuru Watanabe
    • Organizer
      2024 Annual Meeting of the Taiwan Neuroimmunology Medical Society.
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多発性硬化症におけるγδ型T細胞の病態関与と治療反応性バイオマーカーとしての有用性の検討2023

    • Author(s)
      渡邉 充, 松尾 江梨子, 篠田 紘司, 田中 栄蔵, 小栁 文乃, 福元 尚子, 眞﨑 勝久, 松下 拓也, 吉良 潤一, 磯部 紀子
    • Organizer
      第35回日本神経免疫学会学術集会
    • Related Report
      2023 Research-status Report
  • [Presentation] Dimethyl fumarate treatment showed unique change of γδ T cell subsets in multiple sclerosis patients2022

    • Author(s)
      Mitsuru Watanabe, Eriko Matsuo, Shoko Fukumoto, Eizo Tanaka, Katsuhisa Masaki, Takuya Matsushita, Jun-ichi Kira, Noriko Isobe
    • Organizer
      第63回日本神経学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Association between HLA subtype and efficacy of glatiramer acetate in Japanese multiple sclerosis.2022

    • Author(s)
      Eizo Tanaka, Mitsuru Watanabe, Shoko Fukumoto, Katsuhisa Masaki, Takuya Matsushita, Noriko Isobe
    • Organizer
      第63回日本神経学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Low gray matter volume can predict cognitive decline in Japanese patients with multiple sclerosis.2022

    • Author(s)
      Shoko Fukumoto, Mitsuru Watanabe, Masaaki Niino, Katsuhisa Masaki, Takuya Matsushita, Ayako Sakoda, Fumie Hayashi, Jun-ichi Kira, Noriko Isobe
    • Organizer
      第63回日本神経学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Factors Associated with Glatiramer Acetate Efficacy in Japanese Multiple Sclerosis.2022

    • Author(s)
      Eizo Tanaka, Mitsuru Watanabe, Shoko Fukumoto, Koki Suezumi, Katsuhisa Masaki, Takuya Matsushita, Noriko Isobe.
    • Organizer
      14th Congress of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS)
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 日本人多発性硬化症患者におけるグラチラマー酢酸塩の有効性に関与する因子の検討.2022

    • Author(s)
      田中栄蔵, 渡邉充, 福元尚子, 眞﨑勝久, 松下拓也, 磯部紀子
    • Organizer
      第34回日本神経免疫学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 日本人多発性硬化症患者における高次脳機能とMRIパラメータ変化との関連.2022

    • Author(s)
      福元尚子, 渡邉充, 新野正明, 松下拓也, 眞﨑勝久, 迫田礼子, 林史恵, 吉良潤一, 磯部紀子
    • Organizer
      第34回日本神経免疫学会学術大会
    • Related Report
      2022 Research-status Report
  • [Patent(Industrial Property Rights)] クローン性造血による神経免疫疾患の発症予測2024

    • Inventor(s)
      岡田随象、奥野龍禎、渡邉充ら(ほか7人)
    • Industrial Property Rights Holder
      岡田随象、奥野龍禎、渡邉充ら(ほか7人)
    • Industrial Property Rights Type
      特許
    • Filing Date
      2024
    • Related Report
      2024 Annual Research Report

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Published: 2022-04-19   Modified: 2026-01-16  

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