Rapid clearance of psoriatic skin lesions induced by topical cyclopamine. A preliminary proof of concept study.
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.


CONCLUSIONS
An effective treatment for psoriasis is described, consistent with intervention in a proximal/key pathogenic event.
Yasemin Sokak No. 6, Narlidere, Manavkuyu Mahallesi 244 Sokak, 5-1/2 Bornova, Izmir, Turkey.
Sinan
S
Taş
Oktay
O
Avci
D000287:Administration, Topical; D000328:Adult; D001707:Biopsy, Needle; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology*; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014704:Veratrum Alkaloids / Q000008:administration & dosage*
D014704:Veratrum Alkaloids; C000541:cyclopamine