title: Diphencyprone Treatment of Alopecia Areata: Postulated Mechanism of Action and Prospects for Therapeutic Synergy with RNA Interference.
abstract: Diphencyprone (DPCP) is a potent topical sensitizing agent that has been used since the late 1970s by physicians for the treatment of alopecia areata (AA), viral warts (human papillomavirus) and cutaneous metastases of melanoma. Although to date the compound is not approved as a drug by the FDA or EMA, physicians have continued to use DPCP because of its proven effects in these dermatological conditions. The use of the drug has been highly variable because of differences in compounding, and as a result, the literature reports vary widely in the concentrations used for sensitization and challenge treatment with DPCP. The efficacy of DPCP has generally been ascribed to immunological reactions by the host. Inducing inflammation with a contact sensitizer is counterintuitive to treating AA, an autoimmune disorder. We have hypothesized that the body's attempt to downregulate the inflammation caused by the contact sensitizer may also ameliorate AA. Studies using microarray and miRNA profiling may provide information about how DPCP induces inflammation in human skin at different times. Gene targets and microRNAs identified through these data may be modulated by an RNA interference approach to enhance DPCP efficacy and response rates. In addition, this approach may result in the discovery and development of drugs that are more potent and selective for the treatment of AA.
authors.affiliation: RXi Pharmaceuticals, Marlborough, Massachusetts, USA.
authors.forename: Karen G
authors.initials: KG
authors.lastname: Bulock
authors.affiliation: RXi Pharmaceuticals, Marlborough, Massachusetts, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Cardia
authors.affiliation: RXi Pharmaceuticals, Marlborough, Massachusetts, USA.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Pavco
authors.affiliation: Department of Dermatology, NYU School of Medicine, New York, New York, USA.|Hapten Pharmaceuticals, LLC, New York, New York, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Levis
mesh_terms: D000506:Alopecia Areata / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy; D003131:Combined Modality Therapy; D003521:Cyclopropanes / Q000494:pharmacology* / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics*; D034622:RNA Interference; D015854:Up-Regulation
chemical_list: D003521:Cyclopropanes; D003879:Dermatologic Agents; C029402:diphenylcyclopropenone