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Mechanism of Neuronal Damage by virus-infected cells in HAM/TSP.

Research Project

Project/Area Number 19K08004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Araya Natsumi  聖マリアンナ医科大学, 医学研究科, 助教 (80440353)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsHTLV-1 / HTLV-1関連脊髄症(HAM) / 神経障害 / Tax / HTLV-1関連脊髄症 / 中枢神経
Outline of Research at the Start

HAMの主病態は、HTLV-1感染細胞に起因した脊髄の慢性炎症による神経傷害と変性であり、感染細胞の詳細な解析はHAM病態の理解及びその制御に必須である。これまでに研究代表者はHTLV-1感染細胞による炎症の慢性化機構を明らかにし、さらに、炎症部で生じる神経傷害メカニズムの解明を目指している。
研究代表者は、HTLV-1感染細胞を主に含むHAM患者CD4+T細胞における中枢神経再生阻害因子の過剰発現の発見より、その因子が有する神経傷害活性に着目し、本研究では、HTLV-1感染細胞に発現する中枢神経再生阻害因子を介したHAMの神経細胞傷害機構を究明し、HAM脊髄の神経傷害を標的とした新規治療法開発への基盤構築を目的とする。

Outline of Final Research Achievements

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare neurodegenerative chronic inflammatory disease clearly caused by HTLV-1 retroviral infection. However, the direct evidence by which HTLV-1-induced hyperactive immune response induce the central nervous system damage has not yet been demonstrated. This study is the first to demonstrate that HTLV-1-infected cells in HAM/TSP patients contribute not only to chronic inflammation but also to neural cell damage. We also identified a factor that plays an important role in neuronal damage by HTLV-1-infected cells. Therefore, this study could suggest a new therapeutic strategy for HAM/TSP that targets neuropathy mediated by this factor.

Academic Significance and Societal Importance of the Research Achievements

これまで、HAMの治療薬開発はHAMの感染細胞や慢性炎症に対する探索や評価に限られていたが、本研究成果によりHAMの神経障害機構が明らかになることにより、治療戦略として新たに神経障害の抑制を標的とした新薬開発が可能となる。従って、学術的にも臨床的にも重要な課題の解決に結びつく成果になると考える。また、HAMは先進国の中でその患者が多いのは日本のみであるため、HAMの病態や発症予防法・治療法に関する我が国での研究成果は世界中から期待されており、本研究の成果は国際的にも社会貢献という側面からも意義あるものとなる。

Report

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

    (34 results)

All 2022 2021 2020 2019 Other

All Journal Article (14 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Open Access: 8 results) Presentation (17 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (3 results)

  • [Journal Article] Health-related quality of life evaluation using the Short Form-36 in patients with human T-cell leukemia virus type 1-associated myelopathy.2022

    • Author(s)
      Kimura M, Yamauchi J, Sato T, Yagishita N, Araya N, Aratani S, Tanabe K, Horibe E, Watanabe T, Coler-Reilly A, Nagasaka M, Akasu Y, Kaburagi K, Kikuchi T, Shibata S, Matsumoto H, Koseki A, Inoue S, Takata A, Yamano Y.
    • Journal Title

      Front Med

      Volume: in press

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of corticosteroid therapy for HTLV-1-associated myelopathy: A randomized controlled trial (HAMLET-P).2022

    • Author(s)
      Yamauchi J, Tanabe K, Sato T, Nakagawa M, Matsuura E, Tsuboi Y, Tamaki K, Sakima H, Ishihara S, Ohta Y, Matsumoto N, Kono K, Yagishita N, Araya N, Takahashi K, Kunitomo Y, Nagasaka M, Coler-Reilly ALG, Hasegawa Y, Araujo A, Jacobson S, Grassi MFR, Galvao-Castro B, Bland M, Taylor GP, Martin F, Yamano Y.
    • Journal Title

      Viruses

      Volume: in press Issue: 1 Pages: 136-136

    • DOI

      10.3390/v14010136

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical course of neurogenic bladder dysfunction in human T-cell leukemia virus type-1-associated myelopathy/tropical spastic paraparesis: A nationwide registry study in Japan.2021

    • Author(s)
      Iijima N, Yamauchi J, Yagishita N, Araya N, Aratani S, Tanabe K, Sato T, Takata A, Yamano Y.
    • Journal Title

      Orphanet J Rare Dis

      Volume: 16(1) Issue: 1 Pages: 355-355

    • DOI

      10.1186/s13023-021-01990-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An update on human T-cell leukemia virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) focusing on clinical and laboratory biomarkers.2021

    • Author(s)
      Yamauchi J, Araya N, Yagishita N, Sata t, Yamano Y.
    • Journal Title

      Pharmacol Ther

      Volume: 218 Pages: 107669-107669

    • DOI

      10.1016/j.pharmthera.2020.107669

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HTLV-1陽性臓器移植のエビデンス・プラクティスギャップに関する全国アンケート調査.2021

    • Author(s)
      山内淳司, 新谷奈津美, 八木下尚子, 佐藤知雄, 湯沢賢治, 山野嘉久.
    • Journal Title

      移植

      Volume: 56(4) Pages: 377-387

    • NAID

      130008163168

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Mortality and risk of progression to adult T-cell leukemia/lymphoma in HTLV-1-associated myelopathy/tropical spastic paraparesis.2020

    • Author(s)
      Nagasaka M, Yamagishi M, Yagishita N, Araya N, Kobayashi S, Makiyama J, Kubokawa M, Yamauchi J, Hasegawa D, Coler-Reilly ALG, Tsutsumi S, Uemura Y, Arai A, Takata A, Inoue E, Hasegawa Y, Watanabe T, Suzuki Y, Uchimaru K, Sato T, Yamano Y.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 117(21) Issue: 21 Pages: 11685-11691

    • DOI

      10.1073/pnas.1920346117

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Creation and validation of a bladder dysfunction symptom score for HTLV-1-associated myelopathy/tropical spastic paraparesis.2020

    • Author(s)
      Yamakawa N, Yagishita N, Matsuo T, Yamauchi J, Ueno T, Inoue E, Takata A, Nagasaka M, Araya N, Hasegawa D, Coler-Reilly A, Tsutsumi S, Sato T, Araujo A, Casseb J, Gotuzzo E, Jacobson S, Martin F, Puccioni-Sohler M, Taylor GP, Yamano Y; Japan Clinical Research Group on HAM/TSP.
    • Journal Title

      Orphanet J Rare Dis

      Volume: 15(1) Issue: 1 Pages: 175-175

    • DOI

      10.1186/s13023-020-01451-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunophenotypic analysis of cerebrospinal fluid reveals concurrent development of ATL in the CNS of a HAM/TSP patient.2020

    • Author(s)
      Takeda R, Ishigaki T, Ohno N, Yokoyama K, Kawamata T, Fukuyama T, Araya N, Yamano Y, Uchimaru K, Tojo A.
    • Journal Title

      Int J Hematol

      Volume: 111(6) Issue: 6 Pages: 891-896

    • DOI

      10.1007/s12185-019-02815-7

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HTLV-1関連脊髄症(HAM)の病態.2020

    • Author(s)
      新谷奈津美, 山野嘉久.
    • Journal Title

      別冊BIO Clinica 神経疾患と慢性炎症

      Volume: 9(2) Pages: 29-33

    • Related Report
      2020 Research-status Report
  • [Journal Article] Mortality and risk of progression to adult T-cell leukemia/lymphoma in HTLV-1-associated myelopathy/tropical spastic paraparesis.2020

    • Author(s)
      Nagasaka M, Yamagishi M, Yagishita N, Araya N, Kobayashi S, Makiyama J, Kubokawa M, Yamauchi J, Hasegawa D, Coler-Reilly ALG, Tsutsumi S, Uemura Y, Arai A, Takata A, Inoue E, Hasegawa Y, Watanabe T, Suzuki Y, Uchimaru K, Sato T, Yamano Y.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: in press

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Use of cerebrospinal fluid CXCL10 and neopterin as biomarkers in HTLV-1-associated myelopathy/tropical spastic paraparesis treated with steroids2019

    • Author(s)
      Yamauchi Junji、Sato Tomoo、Yagishita Naoko、Araya Natsumi、Hasegawa Daisuke、Tsutsumi Shuntaro、Nagasaka Misako、Coler-Reilly Ariella、Inoue Eisuke、Takata Ayako、Hasegawa Yasuhiro、Yamano Yoshihisa
    • Journal Title

      Journal of Neurology, Neurosurgery & Psychiatry

      Volume: 91 Issue: 3 Pages: 321-323

    • DOI

      10.1136/jnnp-2019-321955

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach2019

    • Author(s)
      Katsuya H, Islam S, Tan, Ito J, Miyazato P, Matsuo, Inada Y, Iwase, Uchiyama Yoshikazu、Hata Hiroyuki、Sato T, Yagishita N, Araya N, Ueno T, Nosaka K, Tokunaga M, Yamagishi M, Watanabe T, Uchimaru K, Fujisawa J-i, Utsunomiya A, Yamano Y, Satou Y
    • Journal Title

      Cell Reports

      Volume: 29 Issue: 3 Pages: 724-735

    • DOI

      10.1016/j.celrep.2019.09.016

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Real-world clinical course of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Japan2019

    • Author(s)
      Tsutsumi Shuntaro、Sato Tomoo、Yagishita Naoko、Yamauchi Junji、Araya Natsumi、Hasegawa Daisuke、Nagasaka Misako、Coler-Reilly Ariella L. G.、Inoue Eisuke、Takata Ayako、Yamano Yoshihisa
    • Journal Title

      Orphanet Journal of Rare Diseases

      Volume: 14 Issue: 1 Pages: 61-61

    • DOI

      10.1186/s13023-019-1212-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cerebrospinal Fluid CXCL10 as a Candidate Surrogate Marker for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.2019

    • Author(s)
      Tamaki K, Sato T, Tsugawa J, Fujioka S, Yagishita N, Araya N, Yamauchi J, Coler-Reilly A, Nagasaka M, Hasegawa Y, Yamano Y, Tsuboi Y.
    • Journal Title

      Front Microbiol

      Volume: 10 Pages: 2110-2110

    • DOI

      10.3389/fmicb.2019.02110

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] HTLV-1陽性臓器移植の診療に関する全国調査.2021

    • Author(s)
      山内淳司、新谷奈津美、八木下尚子、佐藤知雄、湯沢賢治、山野嘉久.
    • Organizer
      第55回日本臨床腎移植学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] HTLV-1関連脊髄症(HAM)における神経障害機構の解析.2021

    • Author(s)
      新谷奈津美、荒谷聡子、八木下尚子、山内淳司、佐藤知雄、山野嘉久.
    • Organizer
      第7回日本HTLV-1学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 全血を用いた改変HTLV-1プロウイルス量定量法に関する検討.2021

    • Author(s)
      佐藤知雄、八木下尚子、新谷奈津美、荒谷聡子、山内淳司、高橋克典、國友康夫、長谷川由美子、東久世裕太、宮地恵子、佐藤賢文、直亨則、斎藤益満、山野嘉久.
    • Organizer
      第7回日本HTLV-1学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] HTLV-1陽性の臓器移植に関する全国アンケート調査.2021

    • Author(s)
      山内淳司、新谷奈津美、八木下尚子、佐藤知雄、湯沢賢治、山野嘉久.
    • Organizer
      第7回日本HTLV-1学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] リアルワールドデータにより示されたHAMの排尿障害に対するミラベグロンの有用性.2021

    • Author(s)
      飯島直樹, 山内淳司, 髙梨世子, 太刀川慶史, 八木下尚子, 新谷奈津美, 荒谷聡子, 田辺健一郎, 佐藤知雄, 高田礼子, 山野嘉久.
    • Organizer
      第7回日本HTLV-1学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] HTLV-1による神経障害機構.2021

    • Author(s)
      新谷奈津美, 荒谷聡子, 八木下尚子, 山内淳司, 佐藤知雄, 山野嘉久.
    • Organizer
      第25回日本神経感染症学会総会・学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] HTLV-1関連脊髄症(HAM)の神経障害機構2021

    • Author(s)
      新谷奈津美, 荒谷聡子, 八木下尚子, 山内淳司, 佐藤知雄, 山野嘉久.
    • Organizer
      第62回日本神経学会学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] リアルワールドデータにより示されたHAMの排尿障害に対するミラベグロンの有用性.2021

    • Author(s)
      飯島直樹, 山内淳司, 八木下尚子, 新谷奈津美, 荒谷聡子, 田辺健一郎, 佐藤知雄, 高田礼子, 山野嘉久.
    • Organizer
      第62回日本神経学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] HAM診療ガイドラインの活用実態および内容の評価に関する全国調査2020

    • Author(s)
      佐藤知雄, 山内淳司, 新谷奈津美, 高橋克典, 國友康夫, 八木下尚子, 山野嘉久.
    • Organizer
      第32回日本神経免疫学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Progress report on a long-term study of anti-CCR4 antibody (mogamulizumab) in patients with HAM/TSP.2019

    • Author(s)
      Sato T, Yagishita N, Araya N, Yamauchi J, Inoue E, Matsumoto N, Hasegawa Y, Yamano Y.
    • Organizer
      The 19th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transcriptomic and epigenomic characteristics of HTLV-1-infected cells in asymptomatic carriers, HAM/TSP, and ATL.2019

    • Author(s)
      Yamagishi M, Kobayashi S, Makiyama J, Araya N, Nakashima M,Iwanaga M, Utsunomiya A, Tanaka Y, Watanabe T, Yamano Y, Uchimaru K.
    • Organizer
      The 19th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] HAM患者における短期の歩行機能変化の指標としての髄液CXCL10およびネオプテリンの有用性2019

    • Author(s)
      山内淳司, 佐藤知雄, 八木下尚子, 新谷奈津美, 井上永介, 山野嘉久.
    • Organizer
      第6回日本HTLV-1学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] HTLV-1感染細胞におけるIFN-JAK1-STAT1経路の機能的意義2019

    • Author(s)
      滝澤絵梨菜、山岸誠、石崎伊純、志賀遥菜、中島誠、新谷奈津美、宇都宮與、中村龍文、田中勇悦、山野嘉久、渡邉俊樹、内丸薫.
    • Organizer
      第6回日本HTLV-1学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] HTLV-1感染初期においてTaxが宿主に与える影響の解析2019

    • Author(s)
      水池潤、山岸誠、小林誠一郎、中島誠、新谷奈津美、牧山純也、宇都宮與、田中勇悦、渡邉俊樹、山野嘉久、内丸薫.
    • Organizer
      第6回日本HTLV-1学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] HAM患者レジストリより収集分析されたHAM患者のリアルワールドデータ.2019

    • Author(s)
      佐藤知雄、八木下尚子、山内淳司、堤俊太郎、新谷奈津美、井上永介、高田礼子、山野嘉久.
    • Organizer
      第31回日本神経免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] HTLV-1関連脊髄症のヒストリカルコントロールとして利用可能な病歴データの収集分析2019

    • Author(s)
      佐藤知雄、八木下尚子、山内淳司、堤俊太郎、新谷奈津美、井上永介、高田礼子、山野嘉久.
    • Organizer
      第37回日本神経治療学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] HAMの短期歩行機能変化の指標としての髄液CXCL10およびネオプテリンの有用性2019

    • Author(s)
      山内淳司, 佐藤知雄, 八木下尚子, 新谷奈津美, 井上永介, 山野嘉久.
    • Organizer
      第37回日本神経治療学会学術集会
    • Related Report
      2019 Research-status Report
  • [Remarks] 聖マリアンナ医科大学 難病治療研究センター

    • URL

      https://nanchiken.jp/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 聖マリアンナ医科大学 難病治療研究センター

    • URL

      http://nanchiken.jp/

    • Related Report
      2020 Research-status Report
  • [Remarks] 難病治療研究センター

    • URL

      http://nanchiken.jp/

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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