Elucidation of the therapeutic effect and mechanism of botulinum toxin on skin sclerosis in systemic sclerosis

• Project/Area Number: 18K16019
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Gunma University
• Principal Investigator: Sekiguchi Akiko 群馬大学, 医学部附属病院, 医員 (60774396)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 全身性強皮症 / 皮膚硬化 / ボツリヌス毒素 / 線維化

Outline of Final Research Achievements

Systemic sclerosis is an intractable disease of unknown cause that causes fibrosis (sclerosis) of the skin and organs and vascular and immune abnormalities. Recently, botulinum toxin has been shown to regulate various cellular functions, including immune function and fibroblast proliferative capacity. In this study, the therapeutic effects of botulinum toxin on the pathogenesis (skin fibrosis, vasculopathy) of bleomycin-induced scleroderma in a mouse model of the disease are investigated and the mechanism is being elucidated. The effect of botulinum toxin on oxidative stress disorder was also investigated. The results of this study may lead to the development of new treatments for skin fibrosis in systemic sclerosis.

Academic Significance and Societal Importance of the Research Achievements

本研究成果によって、ボツリヌス毒素が強皮症の2つの主要病態（皮膚硬化と末梢循環障害）を改善できる画期的な治療薬となる可能性が期待できる。本邦では、ボツリヌス毒素がすでに様々な疾患（腋窩多汗症など）で保険適応を持っており、本研究成果を発展させて、強皮症の血管障害と皮膚硬化に対する適応拡大を目指すことができる。

Research Products

• [Presentation] Inhibitory effect of botulinum toxin B on bleomycin-induced skin fibrosis in mice: Possible regulation of oxidative stress (2019)
  • Author(s): Hritu Baral, Akiko Sekiguchi, Yuta Inoue, Syahla Nisaa Amalia, Sahori Yamazaki, Chisako Fujiwara, Akihiko Uchiyama, Sachiko Ogino, Yoko Yokoyama, Ryoko Torii, Mari Hosoi, Osamu Ishikawa, and Sei-ichiro Motegi
  • Organizer: The 44th Annual Meeting of the Japanese Society for Investigative Dermatology.
  • Int'l Joint Research