Creating melanocompetence in Caucasians

May 1, 2006

San Francisco - Results of a placebo-controlled study undertaken by Australian researchers demonstrate for the first time the ability of treatment with a synthetic melanin-inducing hormone to provide UV protection.

San Francisco - Results of a placebo-controlled study undertaken by Australian researchers demonstrate for the first time the ability of treatment with a synthetic melanin-inducing hormone to provide UV protection.

The investigation was reported by Ross StC. Barnetson, M.D., professor of dermatology, University of Sydney, Australia, and colleagues at the 64th Annual Meeting of the American Academy of Dermatology (AAD), here.

The researchers treated a total of 79 Caucasian subjects with Fitzpatrick skin phototypes I through IV with a series of three 10-day cycles of a synthetic alpha-melanocyte stimulating hormone (alpha-MSH) derivative (CUV1647, Clinuvel Pharmaceuticals) (59 subjects) or placebo (20 subjects). In each cycle, a bolus subcutaneous injection was administered daily on five consecutive days a week for two weeks, and the next treatment cycle started 17 days after the last injection.

Ongoing studies are now using an injected depot preparation that has been associated with improved safety and tolerability. In the initial trial, 12 (20 percent) of 59 subjects treated with the alpha-MSH derivative withdrew because of nausea or flushing.

"Melanin affords natural protection against the damaging effects of UV radiation, but unfortunately, initiation of its synthetic pathway depends on UVR-induced intracellular damage of keratinocytes and melanocytes. Our study results suggest treatment with this synthetic melanotropin may offer a safe method to provide UV protection to Caucasians with Fitzpatrick skin types I and II by stimulating the skin's natural photoprotective mechanism," Dr. Barnetson says.

"In light of the continuing deterioration of the ozone layer, especially in Australia, and the rising incidence of skin cancer, treatment with a synthetic alpha-MSH derivative may represent an extremely important addition to our existing strategies for sun protection. In particular, it may have value in treating persons with photodermatoses, such as polymorphic light eruption. However, it may also have a potential role for increasing skin protection against UV exposure in fair-skinned individuals planning a beach vacation."

Objective parameters for efficacy

To assess changes in skin pigmentation as a measure of cutaneous melanin induction, skin reflectance measurements were obtained from the forehead, cheeks, neck, scapula, inner upper arm, forearm, abdomen and calf in all subjects.

The results were reported as melanin density (MD) and averaged for all eight sites. The subjects were divided into two groups (low and high MED) according to their baseline MD level using a cut-off of 3.5 units.

"MD is equivalent to the epidermal melanin intensity as routinely determined by optical density measurement of light microscopy sections stained for melanin granules, and in Caucasians, it generally ranges from one to five density units. The three and-a-half unit cut-off for defining the two skin type groups in this study was somewhat arbitrary, but essentially divided the subjects into two subsets representing Fitzpatrick phototypes I/II and III/IV skin," Dr. Barnetson explains.