L-08   OLD WINE IN NEW BOTTLES: REVIVING OLD THERAPIES FOR ALOPECIA AREATA

J. Shapiro, L. Tang, J. Sundberg*, H. Lui. University of British Columbia Hair Research and Treatment Centre, Vancouver General Hospital, Vancouver, BC, Canada. *The Jackson Laboratory, Bar Harbor, Maine, USA

Introduction: Alopecia areata (AA) is regarded as a tissue restricted autoimmune disease of hair follicles in which follicular activity is arrested due to the continued activity of a lymphocytic cellular infiltrate. The use of valid animal models provide a tool to dissect out molecular mechanisms of therapeutic effects. Time-honored dermatologic treatments such as anthralin and mechlorethamine have been used in the treatment of AA, but efficacy and mechanism of action has not been studied in any great detail. Methods: Mice and rats with alopecia areata were treated topically with anthralin and mechlorethamine on one side of the dorsal surface. RNAase protection assay, RT-PCR, genomic and proteomic analysis were performed on both treated and non-treated sides. Humans were also treated in a unilateral manner with both agents. Results and Conclusions: All rats and mice responded to topical treatment. Twenty to twenty five percent of humans responded to the above treatments. In the animal models, certain cytokines were consistently upregulated (IL-1 alpha/beta, IL-10) or down-regulated (IFN-alpha and TNF-alpha). Genomic profiling also showed modifications of expression of certain genes. Immunohistochemistry showed migration or total depletion of folliculocentric CD8 and CD4 populations. CD54 or ICAM-1 showed similar changes. Proteomics showed certain proteins related to cellular proliferation or apoptosis were altered. Studying the molecular mechanisms regulating follicular activity in animal models using some of these time-honored dermatologic treatments can potentially give us insight with respect to mechanism of action. Targeting specific cytokines such as IFN-alpha and TNF-alpha using the new biologics may have great potential in the treatment of AA. These visible, accessible, and unilaterally treated animal model systems are ideal to study novel AA therapies as well as the in vivo molecular mechanisms of therapeutic actions.