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Study of inflammatory loop mechanism caused by virus-infected cells in HAM pathogenesis.

Research Project

Project/Area Number 16K09701
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
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)

Research Collaborator Takahashi Katsunori  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsHTLV-1 / HAM / CXCL10 / CXCR3 / 炎症
Outline of Final Research Achievements

From recent our studies, we suggested that the cross-talk between HTLV-1-infected cells and CXCL10 produced from astrocytes in the spinal cord is important for the formation and maintenance of HTLV-1-related myelopathy (HAM). In this study, to test this hypothesis, I analyzed the HAM model mice which were created by implanting HAM-PBMC into the most highly immunodeficient mice that express CXCL10 specifically in the central nervous system (HAM-PBMC-NSG/GFAP-CXCL10 mice). As results, I proved the infiltration of lymphocytes and infected cells into the central nervous system in HAM-PBMC-NSG/GFAP-CXCL10 mice.
In the future, we intend to prove the usefulness as a HAM disease state analysis model by establishing the similarities between the mouse and the HAM disease state by detailed analysis.

Academic Significance and Societal Importance of the Research Achievements

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その責任は重い。未だHAMには有効な治療法が無く、新規治療薬開発が強く要望されている。HAM 治療法の開発には、ヒトのHAM病態を忠実に再現した動物モデルの必要性が高い。これまでに感染T細胞の細胞浸潤に起因する脊髄障害をきたすHAM病態を再現した動物は得られていない。本研究では、世界初のヒト免疫系を再現したHAMモデルマウスの作製を目指し、HAM病態機序の解明、疾患の診断、予防、治療法の発展に寄与したいと考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (32 results)

All 2018 2017 2016 Other

All Journal Article (7 results) (of which Peer Reviewed: 4 results,  Open Access: 5 results) Presentation (21 results) (of which Int'l Joint Research: 9 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Proposal of Classification Criteria for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Disease Activity.2018

    • Author(s)
      Sato T, Yagishita N, Tamaki K, Inoue E, Hasegawa D, Nagasaka M, Suzuki H, Araya N, Ariella Coler-Reilly, Hasegawa Y, Tsuboi Y, Takata A, Yamano Y.
    • Journal Title

      Front Microbiol

      Volume: 25(9) Pages: 1651-1651

    • DOI

      10.3389/fmicb.2018.01651

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HTLV-1関連脊髄症(HAM)の病態・診断・治療.2018

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

      神経内科

      Volume: 89(3) Pages: 297-303

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Mogamulizumab (Anti-CCR4) in HTLV-1-Associated Myelopathy.2018

    • Author(s)
      Sato T, Coler-Reilly ALG, Yagishita N, Araya N, Inoue E, Furuta R, Watanabe T, Uchimaru K, Matsuoka M, Matsumoto N, Hasegawa Y, Yamano Y.
    • Journal Title

      N Engl J Med.

      Volume: 378(6) Issue: 6 Pages: 529-538

    • DOI

      10.1056/nejmoa1704827

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effectiveness of Daily Prednisolone to Slow Progression of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: A Multi-Center Retrospective Cohort Study.2017

    • Author(s)
      Coler-Reilly ALG, Sato T, Matsuzaki T, Nakagawa M, Niino M, Nagai M, Nakamura T, Takenouchi N, Araya N, Yagishita N, Inoue E, Yamano Y.
    • Journal Title

      Neurotherapeutics

      Volume: 14(4) Issue: 4 Pages: 1084-1094

    • DOI

      10.1007/s13311-017-0533-z

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HTLV-1関連脊髄症(HAM)の分子病態と治療.2017

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

      血液内科

      Volume: 74(3) Pages: 373-379

    • Related Report
      2016 Research-status Report
  • [Journal Article] Developing novel treatments for HTLV-1-associated myelopathy (HAM) by investigating molecular pathomechanisms2016

    • Author(s)
      新谷奈津美, 佐藤知雄, アリエラ・コラライリー, 八木下尚子, 山野嘉久.
    • Journal Title

      Japanese Journal of Clinical Immunology

      Volume: 39 Issue: 3 Pages: 207-212

    • DOI

      10.2177/jsci.39.207

    • NAID

      130005157506

    • ISSN
      0911-4300, 1349-7413
    • Related Report
      2016 Research-status Report
    • Open Access
  • [Journal Article] Nation-wide epidemiological study of Japanese patients with rare viral myelopathy using novel registration system (HAM-net).2016

    • Author(s)
      Coler-Reilly ALG, Yagishita N, Suzuki H, Sato T, Araya N, Inoue E, Takata A, Yamano Y.
    • Journal Title

      Orphanet Journal of Rare Diseases

      Volume: 11(1) Issue: 1 Pages: 69-69

    • DOI

      10.1186/s13023-016-0451-x

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] HAM患者に対する抗CCR4抗体製剤(モガムリズマブ)の安全性と有効性.2018

    • Author(s)
      佐藤知雄、八木下尚子、新谷奈津美、井上永介、古田梨愛、渡邉俊樹、内丸薫、松岡雅雄、松本直樹、長谷川泰弘、山野嘉久.
    • Organizer
      第5回日本HTLV-1学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腎移植におけるHTLV-1感染症の危険性.2018

    • Author(s)
      山内淳司、山野嘉久、佐藤知雄、八木下尚子、新谷奈津美、松岡雅雄、市丸直嗣、錦戸雅春、柴垣有吾、杉谷 篤、中村信之、三重野牧子、湯沢賢治.
    • Organizer
      第5回日本HTLV-1学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HTLV-1関連脊髄症に対する抗CCR4抗体製剤(モガムリズマブ)の医師主導治験.2018

    • Author(s)
      佐藤知雄、八木下尚子、新谷奈津美、井上永介、古田梨愛、渡邉俊樹、内丸薫、松岡雅雄、松本直樹、長谷川泰弘、山野嘉久.
    • Organizer
      第30回日本神経免疫学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HTLV-1陽性臓器移植患者レジストリの構築.2018

    • Author(s)
      山内淳司、山野嘉久、佐藤知雄、八木下尚子、新谷奈津美、松岡雅雄、市丸直嗣、錦戸雅春、柴垣有吾、杉谷 篤、中村信之、三重野牧子、湯沢賢治.
    • Organizer
      第54回日本移植学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HAM治療薬としての抗CCR4抗体製剤(モガムリズマブ).2018

    • Author(s)
      佐藤知雄、八木下尚子、新谷奈津美、井上永介、古田梨愛、渡邉俊樹、内丸薫、松岡雅雄、松本直樹、長谷川泰弘、山野嘉久.
    • Organizer
      第23回日本神経感染症学会総会・学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腎移植患者のHTLV-1関連疾患発症に関する全国調査.2018

    • Author(s)
      山内淳司、山野嘉久、佐藤知雄、八木下尚子、新谷奈津美、松岡雅雄、市丸直嗣、錦戸雅春、柴垣有吾、杉谷 篤、中村信之、三重野牧子、湯沢賢治.
    • Organizer
      第23回日本神経感染症学会総会・学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Prevalence, Incidence, and Evidence of High ATL Risk among HAM/TSP Patients2017

    • Author(s)
      Araya Natsumi, Sato Tomoo, Yagishita Naoko, Ariella Coler-Reilly, Uchimaru Kaoru, Yamano Yoshihisa
    • Organizer
      The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Place of Presentation
      東京都千代田区 〔Grand Arc Hanzomon〕
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Daily Prednisolone Slows the Progression of HAM/TSP2017

    • Author(s)
      Ariella L. G. Coler-Reilly, Sato Tomoo, Matsuzaki Toshio, Nakagawa Masanori, Niino Masaaki, Nagai Masahiro, Nakamura Tatsufumi, Takenouchi Norihiro, Araya natsumi, Yagishita Naoko, Yamano Yoshihisa
    • Organizer
      The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Place of Presentation
      東京都千代田区 〔Grand Arc Hanzomon〕
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of a New Assay for Quantification of HTLV-1 Proviral DNA2017

    • Author(s)
      Higashikuse Yuta, Nagai Go, Araya Natsumi, Yagishita Naoko, Sato Tomoo, Yamano yoshihisa
    • Organizer
      The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Place of Presentation
      東京都千代田区 〔Grand Arc Hanzomon〕
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Progression Patterns of Osame's Motor Disability Score for HAM/TSP Patients2017

    • Author(s)
      Inoue Eisuke, Ariella Coler-Reilly, Araya Natsumi, Yagishita Naoko, Sato Tomoo, Takata Ayako, Yamano Yoshihisa
    • Organizer
      The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Place of Presentation
      東京都千代田区 〔Grand Arc Hanzomon〕
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effectiveness of Low-Dose Oral Prednisolone to Treat and Slow Progression of HAM/TSP: A Nationwide Prospective Cohort Study2017

    • Author(s)
      Sato Tomoo,Inoue Eisuke,Yagishita Naoko,Araya Natsumi,Takata Ayako,Yamano Yoshihisa
    • Organizer
      The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Place of Presentation
      東京都千代田区 〔Grand Arc Hanzomon〕
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Patient Satisfaction Survey for HAM-net Registrants2017

    • Author(s)
      Suzuki Hiroko,Sato Kentaro,Kikuchi Takayuki,Kimura Miyuna,Arifuku Hirotaka,Komita Midori,Shimada Kanade,Seki Kurumi,Tachibana Marika,Yagishita Naoko,Ariella Coler-Reilly,Sato Tomoo,Araya Natsumi,Ishikawa Miho,Koike Mikako,Saito Yumi,Takata Ayako,Yamano Yoshihisa
    • Organizer
      The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Place of Presentation
      東京都千代田区 〔Grand Arc Hanzomon〕
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comparative Transcriptome Analysis of HTLV-1-infected Cells and ATL Cells2017

    • Author(s)
      Yamagishi Makoto, Nakano Kazumi, Fujikawa Dai, Kobayashi Seiichiro, Araya Natsumi, Sato Tomoo, Yagishita Naoko, Iwanaga Masako, Utsunomiya Atae, Tanaka Yuetsu , Yamano Yoshihisa, Watanabe Toshiki, Uchimaru Kaoru
    • Organizer
      The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Place of Presentation
      東京都千代田区 〔Grand Arc Hanzomon〕
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] A New Index Describing Urinary Dysfunction in Patients with Human T-lymphotropic Virus Type 1-associated Myelopathy2017

    • Author(s)
      Yamakawa Natsuko, Amano Saaya, Kawakami Hitomi, Yamashita Hitomi, Yagishita Naoko, Araya Natsumi, Sato Tomoo, Takata Ayako, Matsuo Tomohiro, Yamano Yoshihisa
    • Organizer
      The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Place of Presentation
      東京都千代田区 〔Grand Arc Hanzomon〕
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Phase 1/2a study of Mogamulizumab, an anti-CCR4 monoclonal antibody, in patients with HTLV-1-associated myelopathy (HAM/TSP).2017

    • Author(s)
      Yamano Y, Sato T, A. Coler-Reilly, Yanagisawa N, Araya N, Inoue E, Furuta R, Watanabe T, Uchimaru K, Matsuoka M, Matsumoto N, Hasegawa Y.
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 臨床経過とバイオマーカーに基づくHAMの疾患活動性分類基準の提案.2017

    • Author(s)
      長谷川大輔, 八木下尚子, 井上永介, 新谷奈津美, 髙田 礼子, 長谷川泰弘, 佐藤知雄, 山野嘉久.
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] HTLV-1関連脊髄症(HAM)の新たな運動障害重症度評価指標の提案.2017

    • Author(s)
      八木下尚子, 佐藤知雄, 長谷川大輔, 新谷奈津美, 井上永介, 高田礼子, 山野嘉久.
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] HAM患者レジストリを活用した低用量経口プレドニゾロン維持療法の有効性と安全性に関する検討.2017

    • Author(s)
      佐藤知雄, 井上永介, 八木下尚子, 新谷奈津美, 長谷川大輔, 高田礼子, 山野嘉久.
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] HAM発症から診断までの期間における納の運動障害重症度の経時推移の解析2016

    • Author(s)
      井上永介、Ariella Coler-Reilly、新谷奈津美、八木下尚子、佐藤知雄、高田礼子、山野嘉久
    • Organizer
      第3回日本HTLV-1学会学術集会
    • Place of Presentation
      鹿児島県(鹿児島市)〔鹿児島県市町村自治会館〕
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report
  • [Presentation] HAM患者に対する経口ステロイド維持療法の長期的効果2016

    • Author(s)
      佐藤知雄、Ariella Coler-Reilly、新谷奈津美、八木下尚子、中村龍文、永井将弘、新野正明、竹ノ内徳博、中川正法、松崎敏男、山野嘉久
    • Organizer
      第3回日本HTLV-1学会学術集会
    • Place of Presentation
      鹿児島県(鹿児島市)〔鹿児島県市町村自治会館〕
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report
  • [Presentation] HTLV-1関連脊髄症(HAM)におけるHAS-Flow法を用いたATL発症高危険度患者の予測2016

    • Author(s)
      新谷奈津美、佐藤知雄、八木下尚子、高橋克典、内丸薫、山野嘉久
    • Organizer
      第3回日本HTLV-1学会学術集会
    • Place of Presentation
      鹿児島県(鹿児島市)〔鹿児島県市町村自治会館〕
    • Year and Date
      2016-08-26
    • Related Report
      2016 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

      http://nanchiken.jp/

    • Related Report
      2018 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
      2017 Research-status Report
  • [Remarks] http://nanchiken.jp/byouin/

    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] HTLV-1関連脊髄症を治療することに用いるための医薬組成物2017

    • Inventor(s)
      荒木一司、山野嘉久、新谷奈津美
    • Industrial Property Rights Holder
      荒木一司、山野嘉久、新谷奈津美
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-007887
    • Filing Date
      2017-01-19
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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