Debio 0932, a new oral Hsp90 inhibitor, alleviates psoriasis in a xenograft transplantation model

Acta Derm Venereol. 2014 Nov;94(6):672-6. doi: 10.2340/00015555-1838.

Abstract

Debio 0932 is a novel oral heat shock protein 90 (Hsp90) inhibitor developed for anti-cancer therapy. Surprising-ly, during the first clinical trial, one psoriasis patient experienced complete remission of his skin manifestation. However, a possible therapeutic utility of Hsp90 in psoriasis has not previously been reported. The objective of the present study was to explore the ability of Debio 0932 to alleviate psoriasis in a preclinical model. A psoriasis xenograft transplantation model was employed where skin from 5 psoriasis patients was transplanted onto immunodeficient mice (8 xenografts per donor). Debio 0932 was administered perorally daily for 3 weeks and resulted in significant clinical alleviation of psoriasis by day 11 and reduced epidermal thickness evaluated post-treatment. Alleviation of psoriasis in the psoriasis xenograft transplantation model, which may be due to Hsp90's involvement in signalling pathways that are up-regulated in psoriasis, substantiates a potential role of Debio 0932 in psoriasis treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Animals
  • Benzodioxoles / administration & dosage*
  • Dermatologic Agents / administration & dosage*
  • Disease Models, Animal
  • Female
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / metabolism
  • Heterografts
  • Humans
  • Imidazoles / administration & dosage*
  • Mice, SCID
  • Middle Aged
  • Psoriasis / drug therapy*
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Remission Induction
  • Signal Transduction / drug effects
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Skin Transplantation*
  • Time Factors

Substances

  • Benzodioxoles
  • CUDC 305
  • Dermatologic Agents
  • HSP90 Heat-Shock Proteins
  • Imidazoles