Melanotan-1 (MT-1) is a synthetic super-potent derivative of its natural counterpart, alpha-melanocyte-stimulating hormone, one of a family of hormones that induce pigmentation in the body. According to information in the article, the authors previously demonstrated that MT-1 can induce tanning in human volunteers who are known to tan easily in response to sunlight. All previously reported clinical trials with MT-1 were performed with volunteers who were instructed to avoid sunlight and use sunscreens with a sun-protective factor rating of 30 on all skin sites exposed to the sun. The effect of MT-1 when combined with either sunlight or simulated UV-B radiation had not been tested.
Robert T. Dorr, Ph.D., of the University of Arizona, Tucson, and colleagues performed three phase one clinical trials to demonstrate safety for MT-1 therapy combined with UV-B light or sunlight. In the first study, four subjects were randomized to 0.08 milligrams per kilogram of MT-1 per day administered by injection, and four others received injections of isotonic sodium chloride solution (solution containing the same concentration of salt as normal body fluids) for ten days. It was followed by neck irradiation with UV-B light.
In the second study, 12 subjects received MT-1. The dosage was increased to 0.16 milligrams per kilogram per day for ten days, with UV-B radiation given to a buttock site for five days during or after MT-1 administration. The final study randomized eight subjects to three to five days of sunlight to half of the back, or to sunlight plus 0.16 milligrams per kilogram of MT-1, for five days per week for four weeks.
"The results show that the synthetic super-potent melanotropin, MT-1, can be safely combined with small amounts of UV-B from a solar simulator or with brief exposures to full sunlight," the authors report. "We have further shown that MT-1 can be administered for 20 days over four weeks at a daily dose of 0.16 milligrams per kilogram without producing cumulative, more intense or new adverse effects."
Tanning was achieved in three of four subjects receiving MT-1 in the first study. These subjects also had 47 percent fewer sunburn cells at the irradiated site. More skin sites darkened with the higher dose of MT-1 in the second study. In the third study, there was significantly enhanced tanning in the MT-1 group, and it was maintained at least three weeks longer than the tanning in those who were randomized to sunlight only. The controls required 50 percent more sun exposure time for equivalent tanning.
"There were no pathologic findings at any UV-B or sun-exposed sites in any subject," the authors write. "Toxic effects due to MT-1 were minor, consisting of nausea and transient facial flushing."
"Perhaps the most important observation in the three clinical studies of MT-1 is the observation of marked tanning synergy with the combination of UV-B light (protocol 2) or sunlight (protocol 3)," they suggest. "The degree of skin darkening measured at both light exposed sites was significantly greater than that achieved with UV light, sunlight, or drug alone."
(Arch Dermatol. 2004;140:827-835. Available post-embargo at archdermatol.com)
Editor's Note: The studies were conducted under an Investigator-Sponsored Investigational New Drug Application from the U.S. Food and Drug Administration. Co-author Stuart Humphrey, Ph.D., is the Manager-Clinical Development at EpiTan Ltd., Melbourne, Australia, and provided detailed critiques of the manuscript and analysis of the data. Dr. Dorr is a consultant to EpiTan Ltd. Dr. Dorr and co-authors David S. Alberts, M.D., and Norman Levine, M.D., are shareholders in EpiTan Ltd. These studies were conducted entirely at the Arizona Cancer Center, Tucson, between 1994 and 1996.
To contact Robert T. Dorr, Ph.D., call George Humphrey at 520-626-7301.
For more information, contact JAMA/Archives Media Relations at 312/464-JAMA (5262) or e-mail mediarelations@jama-archives.org .
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Archives of Dermatology