Novel low molecular drugs for inflammatory skin disease by inhibiting Hsp90

• Project/Area Number: 26670528
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Mie University
• Principal Investigator: Kakeda Masato 三重大学, 医学(系)研究科(研究院), 助教 (00422866)
• Co-Investigator(Kenkyū-buntansha): MIZUTANI Hitoshi 三重大学, 大学院医学系研究科, 教授 (30115737) ; YAMANAKA Keiichi 三重大学, 大学院医学系研究科, 准教授 (70314135)
• Research Collaborator: YAMAGIWA Akisa ; Yawalkar Nikhil
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Heat shock protein 90 / 尋常性乾癬

Outline of Final Research Achievements

We conducted a study for developing novel small molecular drugs for a resistant inflammatory skin disease: psoriasis vulgaris. Using the imiquimod-induced psoriasis vulgaris mouse model, topical and systemic administration of Hsp90 inhibitor, which has been already used for the clinical trials of human cancer. The Hsp90 inhibitor administration suppressed the clinical skin symptom scores, swelling of the skin and psoriasis-related cytokines expression. As a result, the present study demonstrated the possibility of a novel therapeutic strategy for psoriasis and related diseases using topical and systemic application of Hsp90 inhibitors.

Research Products

• [Journal Article] "Inflammatory skin march": IL-1-mediated skin inflammation, atopic dermatitis, and psoriasis to cardiovascular events. (2015)
  • Author(s): Yamanaka K, Mizutani H.
  • Journal Title: J Allergy Clin Immunol. Volume: 136 Issue: 3 Pages: 823-824
  • DOI: 10.1016/j.jaci.2015.06.009
  • Peer Reviewed
• [Journal Article] Increased expression of heat shock protein 90 in keratinocytes and mast cells in psoriasis (2014)
  • Author(s): M. Kakeda, M. Arock, C. Schlapbach, N. Yawalkar
  • Journal Title: J Am Acad Dermatol Volume: 70 Issue: 4 Pages: 683-690
  • DOI: 10.1016/j.jaad.2013.12.002
  • Peer Reviewed
• [Journal Article] Innate immune cells express IL-17A/F in acute generalized exanthematous pustulosis and generalized pustular psoriasis (2014)
  • Author(s): M. Kakeda, Christoph Schlapbach, G. Danelon, M. M. Tang, V. Cecchinato, N. Yawalkar, M. Uguccioni
  • Journal Title: Arch Dermatol Res Volume: 306 Issue: 10 Pages: 933-938
  • DOI: 10.1007/s00403-014-1488-0
  • Peer Reviewed
• [Journal Article] Persistent release of IL-1s from skin is associated with systemic cardio-vascular disease, emaciation and systemic amyloidosis: the potential of anti-IL-1 therapy for systemic inflammatory diseases. (2014)
  • Author(s): Yamanaka K, Nakanishi T, Saito H, Maruyama J, Isoda K, Yokochi A, Imanaka-Yoshida K, Tsuda K, Kakeda M, Okamoto R, Fujita S, Iwakura Y, Suzuki N, Ito M, Maruyama K, Gabazza EC, Yoshida T, Shimaoka M, Mizutani H.
  • Journal Title: PLoS One. Volume: 9 Issue: 8 Pages: 104479-104479
  • DOI: 10.1371/journal.pone.0104479
  • Peer Reviewed / Open Access
• [Journal Article] IL-17関連抗体と乾癬 (2014)
  • Author(s): 欠田成人 山中恵一 水谷仁
  • Journal Title: 感染・炎症・免疫 Volume: 44 Pages: 158-161
• [Journal Article] 尋常性乾癬と肥満細胞 (2014)
  • Author(s): 欠田成人 山中恵一 水谷仁
  • Journal Title: Visual Dermatology Volume: 14 Pages: 72-73
• [Presentation] Anti-NXP-2 (MJ) antibody-positive dermatomyositis developing severe dysphagia and immune thrombocytopenic purpura with generalized subcutaneous edema: a case report (2016)
  • Author(s): Kakeda M, Omoto Y, Gyobu M, Habe K, Yamanaka K, Muro Y, and Mizutani H
  • Organizer: EADV Congress
  • Place of Presentation: ウィーン、オーストリア
  • Year and Date: 2016-09-28
• [Presentation] ラモトリギンとアセトアミノフェンによるToxic Epidermal Necrolysisの1例：HLA-B*4403保有例 (2016)
  • Author(s): 欠田成人 森如 尾本陽一 山中恵一 磯田憲一 井上織部 杉本恭子 水谷仁
  • Organizer: 日本アレルギー学会
  • Place of Presentation: 東京国際フォーラム (東京)
  • Year and Date: 2016-06-17
• [Presentation] ITP、四肢の著明な浮腫、嚥下障害を生じた皮膚筋炎の1例 (2016)
  • Author(s): 欠田成人 尾本陽一 刑部全晃 波部幸司 山中恵一 水谷仁
  • Organizer: 日本皮膚科学会総会
  • Place of Presentation: 国立京都国際会館 (京都府・京都市)
  • Year and Date: 2016-06-03
• [Presentation] 免疫グロブリン療法が奏功したToxic Epidermal Necrolysisの1例 (2015)
  • Author(s): 欠田成人 森如 尾本陽一 山中恵一 磯田憲一 井上織部 杉本恭子 水谷仁
  • Organizer: 日本皮膚アレルギー・接触皮膚炎学会
  • Place of Presentation: 島根県民会館 (島根県・松江)
  • Year and Date: 2015-10-31
• [Presentation] IL-36 expression in hidradenitis suppurativa (2015)
  • Author(s): R. Thomi, M. Kakeda, N. Yawalkar, R.E. Hunger
  • Organizer: 96. Jarhesversammlung der SGDV
  • Place of Presentation: バーゼル、スイス
  • Year and Date: 2015-09-04
  • Int'l Joint Research
• [Presentation] 急性汎発性発疹性膿疱症と膿疱性乾癬では、自然免疫細胞がIL-17A/Fを発現する (2015)
  • Author(s): 欠田成人, Christoph Schlapbach, G. Danelon, M. M. Tang, V. Cecchinato, N. Yawalkar, M. Uguccioni
  • Organizer: 日本アレルギー学会
  • Place of Presentation: グランドプリンスホテル新高輪 (東京)
  • Year and Date: 2015-05-26
• [Presentation] Increased expression of heat shock protein 90 in keratinocytes and mast cells in psoriasis (2014)
  • Author(s): M. Kakeda, M. Arock, H. Mizutani, C. Schlapbach, N. Yawalkar
  • Organizer: 23rd EADV Congress
  • Place of Presentation: Amsterdam, The Netherlands
  • Year and Date: 2014-10-08 – 2014-10-12
• [Presentation] 急性汎発性発疹性膿疱症と膿疱性乾癬では自然免疫細胞がIL-17を発現する (2014)
  • Author(s): 欠田 成人, Christoph Schlapbach, Gabriela Danelon, MM Tang, Valentina Cecchinato, Nikhil Yawalkar , and Mariagrazia Uguccioni
  • Organizer: 日本皮膚科学会総会
  • Place of Presentation: 国立京都国際会館 京都
  • Year and Date: 2014-05-30 – 2014-06-01