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	Karen G Bulock, James P Cardia, Pamela A Pavco, William R Levis
Journal	The journal of investigative dermatology. Symposium proceedings (J Investig Dermatol Symp Proc) Vol. 17 Issue 2 Pg. 16-8 (Nov 2015) ISSN: 1529-1774 [Electronic] United States
PMID	26551938 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Cyclopropanes Dermatologic Agents diphenylcyclopropenone
Topics	Alopecia Areata (drug therapy, genetics, immunology) Autoimmune Diseases (drug therapy) Combined Modality Therapy Cyclopropanes (pharmacology, therapeutic use) Dermatologic Agents (pharmacology, therapeutic use) Down-Regulation Gene Expression Regulation (drug effects) Humans Inflammation (drug therapy, genetics) RNA Interference Up-Regulation

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