title: 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.affiliation: Department of Dermatology, Aarhus University Hospital, P. P. Oerumsgade 11, DK-8000 Aarhus, Denmark. Karin.Stenderup@ki.au.dk.
authors.forename: Karin
authors.initials: K
authors.lastname: Stenderup
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rosada
authors.forename: Bruno
authors.initials: B
authors.lastname: Gavillet
authors.forename: Grégoire
authors.initials: G
authors.lastname: Vuagniaux
authors.forename: Tomas Norman
authors.initials: TN
authors.lastname: Dam
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage*; D003879:Dermatologic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D016513:Mice, SCID; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012074:Remission Induction; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016038:Skin Transplantation; D013997:Time Factors
chemical_list: D052117:Benzodioxoles; C543177:CUDC 305; D003879:Dermatologic Agents; D018841:HSP90 Heat-Shock Proteins; D007093:Imidazoles