New topical drug would tan skin without UV exposure

Researchers hope the development will lead to new ways to protect skin against UV-induced damage and cancer formation.

Researchers have developed a way to tan human skin without ultraviolet (UV) radiation and its associated damaging effects. The drug, described in a Cell Reports study, also provided protective tans in red-haired mice, which like red-haired humans, are more susceptible to skin cancer from UV radiation. The drug works by stimulating cells to produce more UV-absorbing pigments. However, more studies are needed before it can be proven safe in humans.

We spoke to senior author David E. Fisher who is the Chief of Dermatology at Massachusetts General Hospital and professor of Dermatology at Harvard Medical School.

ResearchGate: What motivated this study?

David Fisher: Prior data had shown that switching skin pigment from light to dark in laboratory mice, afforded potent protection against UV damage and carcinogenesis. However, this pigment switching could not be achieved in human skin due to the strong barrier function, which is about five times thicker than in mice.

RG: What have you developed? How does it work?

Fisher: We used our detailed knowledge of the signaling pathways controlling pigmentation, to generate a class of chemical compounds that can inhibit an enzyme which antagonizes the pigmentation pathway, thereby stimulating skin pigmentation.

This photograph shows the treatment of human breast skin explants with topical drug that induces pigmentation. Credit: Nisma Mujahid and David E. Fisher.

RG: How did you develop this?

Fisher: Work from other scientists showed that the SIK kinase enzyme inhibits the MITF gene, which controls skin pigmentation. We worked with medicinal chemist Nathanael Gray to generate SIK inhibitors which could penetrate human skin. These agents stimulated MITF and pigmentation both within cells grown in the lab, and when topically applied to human skin within a petri dish.

RG: What kind of applications does this have?

Fisher: We would anticipate, by analogy with studies from mice about 10 years ago that this pigment switch may afford protection against ultraviolet radiation damage and skin cancer risk.

RG: What needs to be done to in order for people to be able to use this? When do you think it could be available?

Fisher: Several key steps are required before application to humans. Most importantly, as with any new agent of this type, safety/toxicity analyses are essential. Studies thus far have not identified challenges along these lines, but one must be cautious with development of new agents of this type. One potential advantage with pigment induction, is that dark melanin typically stays in skin until the epidermal cells naturally slough off the surface after a week or two, as is typical after a tan. For this reason, approaches like this may only require quite limited exposure to agent that stimulates pigmentation, rather than continuous exposure— but these types of questions need to be systematically studied.

RG: What’s next for your research?

Fisher: We are studying exactly these types of questions:  doses, schedules, toxicity, and we are in conversation with potential industry partners or considering a focused company (startup) to further develop the technology.

Featured image courtesy of Mike Wilson.