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Elucidation of the pathogenesis of inclusion body myositis by focusing on the abnormal aggregation protein clearance system

Research Project

Project/Area Number 20K21563
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionTohoku University

Principal Investigator

AOKI Masashi  東北大学, 医学系研究科, 教授 (70302148)

Co-Investigator(Kenkyū-buntansha) 割田 仁  東北大学, 大学病院, 助教 (30400245)
鈴木 直輝  東北大学, 大学病院, 助教 (70451599)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords封入体筋炎 / タンパク異常凝集
Outline of Research at the Start

独自に開発したヒト骨格筋電気収縮培養系を活用し細胞内凝集および細胞外排出されるApoE蛋白を定量評価し、細胞外へのApoE蛋白排出促進を指標にした病態解析を行う。さらには小分子スクリーニングにより骨格筋の凝集体形成蛋白排出システムの鍵分子を明らかにする。ヒト生検筋と病態モデルマウスを用いて細胞モデルの結果を検証することで、異常凝集体の形成機構の全体像に迫る。

Outline of Final Research Achievements

Inclusion body myositis (sIBM) is a chronic, progressive and refractory muscle disease seen in middle-aged and older people. sIBM patients' skeletal muscles show abnormal aggregates such as amyloid-beta, TDP-43 and FUS, suggesting a degenerative disease in the muscle. Using an originally developed human skeletal muscle electrical pulse culture system, we found cytoplasmic deposition of TDP-43, one of the aggregation proteins found in ALS. The results were reported in SciRep journal. Myoblasts were established from three new cases of sIBM muscle biopsies. B-cell follicle in sIBM muscle tissue were also observed in a case. It was summarised and reported in NeuromusDisord journal.

Academic Significance and Societal Importance of the Research Achievements

封入体筋炎は治療法が無く最終的に著明な筋萎縮を来して寝たきりになる難病であり、日本人でも社会の高齢化に伴い、患者数が増加しており、中高年で最も頻度の高い炎症性筋疾患となっている。その病態解明・治療開発は高齢化に伴うサルコペニアやフレイル、廃用性筋萎縮・筋ジストロフィーなどへの治療開発に寄与しうる。本研究により異常蛋白が蓄積するという変性の観点から、封入体筋炎の病態の一旦が明らかになった。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (8 results)

All 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 4 results)

  • [Journal Article] Feeder-supported in vitro exercise model using human satellite cells from patients with sporadic inclusion body myositis2022

    • Author(s)
      Li Yuqing、Chen Weijian、Ogawa Kazumi, ...Suzuki Naoki、Aoki Masashi、Kanzaki Makoto
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1

    • DOI

      10.1038/s41598-022-05029-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A rare case of sporadic inclusion body myositis and rheumatoid arthritis exhibiting ectopic lymphoid follicle-like structures: a case report and literature review.2021

    • Author(s)
      Konomatsu K, Izumi R, Suzuki N, Takai Y, Shirota Y, Saito R, Kuroda H, Aoki M.
    • Journal Title

      Neuromuscul Disord.

      Volume: 31 Issue: 9 Pages: 870-876

    • DOI

      10.1016/j.nmd.2021.07.002

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel deletion in the C-terminal region of HSPB8 in a family with rimmed vacuolar myopathy2021

    • Author(s)
      Inoue-Shibui Aya、Niihori Tetsuya、Kobayashi Michio、Suzuki Naoki、Izumi Rumiko、Warita Hitoshi、Hara Kenju、Shirota Matsuyuki、Funayama Ryo、Nakayama Keiko、Nishino Ichizo、Aoki Masashi、Aoki Yoko
    • Journal Title

      Journal of Human Genetics

      Volume: NA Issue: 10 Pages: 965-972

    • DOI

      10.1038/s10038-021-00916-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy and Safety of Bimagrumab in Sporadic Inclusion Body Myositis2021

    • Author(s)
      Amato Anthony A.、Hanna Michael G.、Machado Pedro M.、、、、Suzuki Naoki、Aoki Masashi、、、on behalf of the RESILIENT Study Extension Group
    • Journal Title

      Neurology

      Volume: 96 Issue: 12

    • DOI

      10.1212/wnl.0000000000011626

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-52020

    • Author(s)
      Oikawa Yoshitsugu、Izumi Rumiko、Koide Masashi、、、Aoki Masashi、Kure Shigeo、Abe Takaaki
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 12 Pages: e0231064-e0231064

    • DOI

      10.1371/journal.pone.0231064

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inducible Rpt3, a Proteasome Component, Knockout in Adult Skeletal Muscle Results in Muscle Atrophy2020

    • Author(s)
      Kitajima Yasuo、Suzuki Naoki、Yoshioka Kiyoshi、Izumi Rumiko、Tateyama Maki、Tashiro Yoshitaka、Takahashi Ryosuke、Aoki Masashi、Ono Yusuke
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8

    • DOI

      10.3389/fcell.2020.00859

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The genetic profile of dysferlinopathy in a cohort of 209 cases: Genotype-phenotype relationship and a hotspot on the inner DysF domain2020

    • Author(s)
      Izumi Rumiko、Takahashi Toshiaki、Suzuki Naoki、Niihori Tetsuya、Ono Hiroya、Nakamura Naoko、Katada Shinichi、Kato Masaaki、Warita Hitoshi、Tateyama Maki、Aoki Yoko、Aoki Masashi
    • Journal Title

      Human Mutation

      Volume: 41 Issue: 9 Pages: 1540-1554

    • DOI

      10.1002/humu.24036

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] AMPK Complex Activation Promotes Sarcolemmal Repair in Dysferlinopathy2020

    • Author(s)
      Ono Hiroya、Suzuki Naoki、Kanno Shin-ichiro、Kawahara Genri、Izumi Rumiko、Takahashi Toshiaki、Kitajima Yasuo、Osana Shion、Nakamura Naoko、Akiyama Tetsuya、Ikeda Kensuke、Shijo Tomomi、Mitsuzawa Shio、Nagatomi Ryoichi、Araki Nobukazu、Yasui Akira、Warita Hitoshi、Hayashi Yukiko K.、Miyake Katsuya、Aoki Masashi
    • Journal Title

      Molecular Therapy

      Volume: 28 Issue: 4 Pages: 1133-1153

    • DOI

      10.1016/j.ymthe.2020.02.006

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2020-08-03   Modified: 2023-01-30  

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