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Research contributing to the diagnosis of inflammatory pathology prior to the onset of HAM with the aim of suppressing the onset of the disease through ultra-early treatment

Research Project

Project/Area Number 21K07418
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionKagoshima University

Principal Investigator

MATSUURA EIJI  鹿児島大学, 医歯学域医学系, 客員研究員 (30598800)

Co-Investigator(Kenkyū-buntansha) 高嶋 博  鹿児島大学, 医歯学域医学系, 教授 (80372803)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsHTLV-1 / HAM/TSP / epidemiology / cytotoxic T lymphocytes / muscle / T cell clone / HTLV‐1 / 診断マーカー / HTLV / キャリア / HAM / 早期診断 / 剖検脊髄 / 病理 / 筋 / CTL / 痙性脊髄麻痺 / HTLV-1キャリア / 疫学 / 発症年齢 / 超早期診断
Outline of Research at the Start

HTLV-1による炎症がHAM発症のかなり以前から生じている事を証明するためにHTLV-1無症候性キャリアにおける脊髄内HTLV-1特異的炎症の存在を証明する。また、診断基準を満たさない患者髄液でも特異的炎症が検出可能な事を証明する。これによりHAM患者に施される治療を無症候性キャリアや感覚・排尿障害だけの患者にまで治療windows opportunityを拡大し, HAM(運動障害)発症を遅延させ得る事を証明する。その為に①無症候性キャリア剖検脊髄内に特異的炎症の存在し②患者レジストリデータを解析し,抗炎症剤等の使用歴がHAM発症時期を遅らせる事を証明する。

Outline of Final Research Achievements

We clarified the infection rate by each generation in each decade from 1920 to the 2000s in Kagoshima Prefecture, and finally reported in the paper that there are 80,000 infected people in the prefecture. We also confirmed virus-specific inflammation within the spinal cord of virus carriers who had not developed HAM (paper in preparation for submission). By analyzing 101 patients, we identified the most affected muscles both in the early and advanced stages of the disease and reported this feature as a diagnostic marker for HAM. We also reported a case of HAM complicated with muscle disease that resembles these characteristics. Genetically, we identified the genetic features of HAM in East Asia. In addition, we identified and characterized T-cell clones that are strongly associated with the development of HAM.

Academic Significance and Societal Importance of the Research Achievements

本研究結果により疫学的に今後大規模疫学調査を行わなくても毎年簡便にキャリア数を推計できるようになった。今回判明したHAM早期診断を可能とするHAMの神経学的特徴と、HAM診断基準を満たす以前の患者の脊髄内のHTLV-1特異的炎症の存在を確認できたことで、臨床症状やバイオマーカーにより超早期診断が可能であることを示すものである。この超早期診断によりHAM診断基準を満たす前の患者(pre-HAM)に早期治療介入できる可能性が明らかとなった。

Report

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

    (13 results)

All 2024 2023 2022 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] NIH/NINDS(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] National Institute of Health(米国)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Geographic characteristics of HTLV-1 molecular subgroups and genetic substitutions in East Asia: Insights from complete genome sequencing of HTLV-1 strains isolated in Taiwan and Japan2024

    • Author(s)
      Nozuma Satoshi、Yoshimura Akiko、Pai Shun-Chung、Chen Hung-Jen、Matsuura Eiji、Tanaka Masakazu、Kodama Daisuke、Dozono Mika、Matsuzaki Toshio、Takashima Hiroshi、Yang Ya-Chien、Kubota Ryuji
    • Journal Title

      PLOS Neglected Tropical Diseases

      Volume: 18 Issue: 2 Pages: e0011928-e0011928

    • DOI

      10.1371/journal.pntd.0011928

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Iliopsoas Muscle Weakness as a Key Diagnostic Marker in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)2023

    • Author(s)
      Matsuura Eiji、Nozuma Satoshi、Dozono Mika、Kodama Daisuke、Tanaka Masakazu、Kubota Ryuji、Takashima Hiroshi
    • Journal Title

      Pathogens

      Volume: 12 Issue: 4 Pages: 592-592

    • DOI

      10.3390/pathogens12040592

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HTLV-1-associated myelopathy/tropical spastic paraplegia with sporadic late-onset nemaline myopathy: a case report2023

    • Author(s)
      Matsuura Eiji、Nozuma Satoshi、Shigehisa Ayano、Dozono Mika、Nakamura Tomonori、Tanaka Masakazu、Kubota Ryuji、Hashiguchi Akihiro、Takashima Hiroshi
    • Journal Title

      BMC Musculoskeletal Disorders

      Volume: 24 Issue: 1 Pages: 355-355

    • DOI

      10.1186/s12891-023-06461-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HTLV-1 関連脊髄症の臨床2023

    • Author(s)
      EIJI MATSUURA
    • Journal Title

      Neuroinfection 28(1): 11-, 2023

      Volume: 28 Pages: 11-14

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Identification and tracking of HTLV-1-infected T cell clones in virus-associated neurologic disease2023

    • Author(s)
      Nozuma S, Matsuura E, Tanaka M, Kodama D, Matsuzaki T, Yoshimura A, Sakiyama Y, Nakahata S, Morishita K, Enose-Akahata Y, Jacoboson S, Kubota R, Takashima H.
    • Journal Title

      JCI Insight.

      Volume: 8 Issue: 7 Pages: 237-245

    • DOI

      10.1172/jci.insight.167422

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficacy of L-Arginine Treatment in Patients with HTLV-1-Associated Neurological Disease.2023

    • Author(s)
      Satoshi Nozuma, Eiji Matsuura, Yuichi Tashiro, Ryusei Nagata, Masahiro Ando, Yu Hiramatsu, Yujiro Higuchi, Yusuke Sakiyama, Akihiro Hashiguchi, Kumiko Michizono, Keiko Higashi, Toshio Matsuzaki, Daisuke Kodama, Masakazu Tanaka, Yoshihisa Yamano, Takashi Moritoyo, Ryuji Kubota, Hiroshi Takashima.
    • Journal Title

      Ann Clin Transl Neurol.

      Volume: 10 Issue: 2 Pages: 237-245

    • DOI

      10.1002/acn3.51715

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High Prevalence of HTLV-1 Carriers Among the Elderly Population in Kagoshima, a Highly Endemic Area in Japan2022

    • Author(s)
      46.Tashiro Y, Matsuura E, Sagara Y, Nozuma S, Kodama D, Tanaka M, Koriyama C, Kubota R, Takashima H.
    • Journal Title

      AIDS Res Hum Retroviruses.

      Volume: 38 Issue: 5 Pages: 363-369

    • DOI

      10.1089/aid.2021.0164

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] ILIOPSOAS MUSCLE WEAKNESS AS A KEY DIAGNOSTIC MARKER IN HTLV-1-ASSOCIATED MYELOPATHY/TROPICAL SPASTIC PARAPARESIS (HAM/TSP)2023

    • Author(s)
      Eiji Matsuura, Yoshida Takashi, Satoshi Nozuma, Mika Dozono, Daisuke Kodama, Masakazu Tanaka, Ryuji Kubota and Hiroshi Takashima
    • Organizer
      26th World Congress of Neurology (WCN)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] HTLV-1関連脊髄症/熱帯性痙性対麻痺(HAM/TSP)の診断マーカーとしての腸腰筋の筋力低下について2023

    • Author(s)
      吉田崇志、松浦英治、野妻智嗣、堂園美香、兒玉大介、田中正和、久保田龍二、髙嶋博
    • Organizer
      第35回日本神経免疫学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ILIOPSOAS MUSCLE WEAKNESS AS A KEY DIAGNOSTIC MARKER IN HTLV-1-ASSOCIATEDMYELOPATHY/TROPICAL SPASTIC PARAPARESIS (HAM/TSP)2023

    • Author(s)
      Eiji Matsuura, Satoshi Nozuma, Mika Dozono, Takashi Yoshida, Daisuke Kodama, Masakazu Tanaka, Ryuji Kubota, Hiroshi Takashima
    • Organizer
      World congress of Neurology
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] HAM診断における腸腰筋の筋力低下の意義2023

    • Author(s)
      松浦英治、野妻智嗣、樋口雄二郎、﨑山祐介、橋口昭大、道園久美子、東桂子、児玉大介、田中正和、久保田龍二、高嶋 博
    • Organizer
      第26回日本神経感染症学会
    • Related Report
      2022 Research-status Report

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

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