Psoriasis is believed by some to be an auto-immune disease, progesterone has immunosuppressive properties, it inhibits the Th1 cytokine response leading to inflammation and stimulates IL-10 which is anti-inflammatory. Vitamin D (1,25(OH) 2D) is one of the most potent substances to inhibit proliferation of both normal and hyperproliferative cells and induce them to mature. 1,25(OH) 2D and its analogs have been developed for treating the hyperproliferative disease psoriasis. Analogs of 1,25(OH)2D are being developed to achieve specificity for non skeletal target tissues such as the parathyroid gland and cancers to avoid the hypercalcemia resulting from 1,25(OH)2D itself. Vitamin D and its metabolites are carried in the blood bound to vitamin D binding protein (DBP) and albumin–for most tissues it is the free (ie. The ability of 1,25(OH)2D to inhibit proliferation and stimulate differentiation has led to the development of a number of analogs in the hopes of treating hyperproliferative disorders such as psoriasis and cancer without raising serum calcium. A number of other autoimmune diseases have been found in animal studies to respond favorably to vitamin D and 1,25(OH)2D or its analogs, and epidemiologic evidence linking vitamin D deficiency to increased incidence of these diseases has been reported. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects. D (1,25(OH)2D) on calcium and phosphate homeostasis from its effects on these other biologic processes and, in particular, to target just one such process. For example, calcipotriol and 22-oxa calcitriol (OCT) are approved for the treatment of psoriasis; paricalcitol, doxercalciferol, and falecalcitriol are approved for secondary hyperparathyroidism (nota bene: OCT and falecalcitriol are approved for use only in Japan). In humans, a leu99pro mutation in CYP2R1 has been found in a Nigerian with severe bone disease associated with biochemical evidence of rickets including a low 25OHD but normal 1,25(OH)2D (Cheng et al.
A topical composition according to claim 1 for the treatment of a hyperproliferative skin disease. Vitamin D3 analogs exert their effects through interaction with vitamin D3 receptor (VDR) located in epidermal keratinocytes 8. Calcipotriol (and 1,25(OH)2D3) has poor penetration through the stratum corneum into the epidermis (internal report) which may explain its limited efficacy and frequently its treatment failures 19-21. Vitamin D analogs like calcipotriol have antipsoriatic effects and might mediate this effect by changing AMP expression. Balancing AMP alarmin expression might be a novel goal in treatment of chronic inflammatory skin diseases.