Rapid Clearance of Psoriatic Skin Lesions Induced by Topical Cyclopamine

Background: We have earlier found a highly efficient induction of the differentiation of epidermal lineage skin tumors by cyclopamine, a steroidal alkaloid inhibitor of the hedgehog/smoothened signaling, under conditions in which cyclopamine exerted no adverse effect on skin. Objective: We aimed to develop a mechanism-based treatment for psoriasis with cyclopamine. Methods: We subjected psoriatic skin lesions to cyclopamine under conditions similar to those we used for skin tumors and evaluated the responses of lesions clinically and by histopathological/immunohistochemical analyses. Results: All treated lesions in different patients having plaque and guttate forms of psoriasis regressed rapidly. Differentiation of the epidermal cells of lesional skin and disappearances of infiltrating inflammatory cells were evident within a day. Lesions were cleared commonly on days 3–4. Former treatment sites followed up for more than 24 months now show a lack of adverse effects in the long term. Conclusion: An effective treatment for psoriasis is described, consistent with intervention in a proximal/key pathogenic event.