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

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.
Authors	Karin Stenderup, Cecilia Rosada, Bruno Gavillet, Grégoire Vuagniaux, Tomas Norman Dam
Journal	Acta dermato-venereologica (Acta Derm Venereol) Vol. 94 Issue 6 Pg. 672-6 (Nov 2014) ISSN: 1651-2057 [Electronic] Sweden
PMID	24604074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Benzodioxoles CUDC 305 Dermatologic Agents HSP90 Heat-Shock Proteins Imidazoles
Topics	Administration, Oral Adult Aged Animals Benzodioxoles (administration & dosage) Dermatologic Agents (administration & dosage) Disease Models, Animal Female HSP90 Heat-Shock Proteins (antagonists & inhibitors, metabolism) Heterografts Humans Imidazoles (administration & dosage) Mice, SCID Middle Aged Psoriasis (drug therapy, metabolism, pathology) Remission Induction Signal Transduction (drug effects) Skin (drug effects, metabolism, pathology) Skin Transplantation Time Factors

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