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Establishment of the novel treatment strategy for systemic sclerosis using anti-fibrotic compound.

Research Project

Project/Area Number 17K16333
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Dermatology
Research InstitutionUniversity of Fukui

Principal Investigator

Koizumi Haruka  福井大学, 学術研究院医学系部門, 特別研究員 (10792088)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords全身性強皮症 / 分子標的治療薬 / 内服治療 / 抗線維化 / 線維芽細胞 / 皮膚 / 肺 / 腎臓 / HPH-15 / ブレオマイシン / 強皮症 / マウスモデル / 線維化 / 皮膚科学 / 膠原病
Outline of Final Research Achievements

We evaluated the therapeutic efficacy of the novel compound HPH-15 in two distinct mice model for systemic sclerosis. Oral application of HPH-15 ameliorates the skin and lung sclerosis in modified GvHD-induced and MHC-mismatched models. In both mice, locally infiltrating lymphocytes and M2-macrophages, as well as alphaSMA-positive myofibroblasts, were decreased in number, together wth the reduced expression levels of collagens and inflammtory cytokines/chemokines. These findings suggest the possible antifibrotic effects of HPH-15 in vivo, which can be a potential candidate of the future treatment option for human systemic sclerosis.

Academic Significance and Societal Importance of the Research Achievements

強皮症の新規治療薬の候補として、他の膠原病などで既に使用されている抗IL-6R抗体や抗CD20抗体などの臨床治験が本症でも行われている。これらは高価なバイオロジクスの注射製剤であり、経口可能な化合物の治療薬が期待されている。HPH-15は実用化された場合に抗体製剤に比べて安価で簡便に使用できる。HPH-15の治療効果がマウスで認められれば、我々の抗線維化薬のスクリーニング法の有用性を実証することができるのみならず、本化合物が線維化や血管障害をきたす様々な疾患の治療薬として拡大する可能性を有している点でも大きな医学貢献に結びつくことが予想される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (2 results)

All 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results)

  • [Journal Article] Successful treatment of recalcitrant subcorneal pustular dermatosis with oral nicotinamide.2019

    • Author(s)
      Yamaguchi Y, Oyama N, Koizumi H, Chino T, Hasegawa M.
    • Journal Title

      J Dermatol

      Volume: 46 Issue: 11

    • DOI

      10.1111/1346-8138.14980

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cladophialophora bantiana infection mimicking neuromyelitis optica.2019

    • Author(s)
      Enomoto S, Shigemi H, Kitazaki Y, Ikawa M, Yamamura O, Hamano T, Tai K, Iwasaki H, Koizumi H, Hasegawa M, Takeda K, Nakamoto Y.
    • Journal Title

      J Neurol Sci.

      Volume: 399: Pages: 169-171

    • DOI

      10.1016/j.jns.2018.12.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed

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Published: 2017-04-28   Modified: 2021-02-19  

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