Clinical potential of Melanotan® (NDP‐α‐MSH) in skin protection – current status and future perspective

Abstract

There is good epidemiological evidence that melanin in the skin protects against sunburn and skin cancer resulting from excessive ultraviolet radiation (UVR) exposure. Melanin is synthesized in a multistep biochemical pathway within specialized cell types in human skin called melanocytes situated in the epidermis. UV light causes an increase in melanocyte‐stimulating hormone (α‐MSH) receptor activity on cutaneous melanocytes (MC1‐R) that results in an increase of eumelanin within the epidermal melanocytes. Melanotan is a synthetic analogue of α‐MSH with potent melanogenic activity in animals and humans. We have recently completed a double‐blind, randomized controlled study in 80 healthy Caucasian adult subjects. A fixed dose of Melanotan (0.16 mg/kg/day) or placebo in a 3 : 1 ratio was given as three cycles of daily subcutaneous injections over 10 days each month for three consecutive months. Changes in skin pigmentation were quantified by serial skin reflectance measurements and UVR injury, as determined by ×3 MED exposure to broadband UVR, was assessed by measurement of apoptosis (sunburn cells). Results demonstrated that a highly significant increase in skin melanin was attained in all subjects on active treatment compared with placebo, and this was especially pronounced in subjects with lighter skin types (Fitzpatrick I and II; P < 0.0001). In these latter subjects, significant sunburn protection was also determined. The ability of Melanotan to stimulate melanin production without the associated UV‐induced skin damage may prove a useful adjunct to current photoprotective strategies to stem the marked rise in skin cancer incidence. Currently, we are studying the therapeutic efficacy of a slow‐release implant of Melanotan in skin disorders such as polymorphic light eruption and psoriasis.