A mild labor inducer could treat the skin condition of vitiligo

Patients with an appearance-altering skin condition may experience relief with an unlikely cocktail of a labor-inducing molecule, an immunosuppressive drug and controlled UVB irradiation.

This discovery led by the College of Veterinary Medicine, published in Natural communicationsuses drugs already approved by the FDA, accelerating the move of a brand new treatment for the disease, vitiligo, to clinical trials.

Vitiligo occurs when the immune system destroys the skin’s melanocytes, the cells that create melanin to give color and protection to the skin. As a result, patients’ skin presents with depigmented white spots, which can lead to social stigma and decreased quality of life.

Most existing medications treat the autoimmune aspect of vitiligo, stopping the destruction of melanocytes. However, these medications rarely result in complete, long-lasting pigmentation of the skin.

“We wanted to find ways to repigment the skin in a more durable and comprehensive way,” said Andrew White, associate professor in the Department of Biomedical Sciences and lead author of the study. To do this, White adopted an approach based on controlled UVB irradiation.

White’s idea was inspired by a 2013 scientific paper detailing how UVB triggers the movement of melanocytes from hair follicles into the skin. However, it was unclear why UVB caused this migration and how to control the process.

“There was basically no protocol for what we were trying to do,” White said.

Luye An, a doctoral student in White’s lab, led the study.

Using mouse models to study the disease, the team exposed the white skin of black-furred mice to UVB and induced the migration of melanocytes from the mice’s follicles into their skin, just like the 2013 study.

However, in this case, the experiments revealed something puzzling: the answer differed between men and women. Initially ignoring the differences between the sexes, the researchers sometimes observed strong migration of melanocytes and sometimes very little, depending on the randomly selected mice.

“At first it was frustrating and confusing,” White said. “Sexual dimorphism was unexpected, but when we figured it out, it was really exciting.”

The team found that UVB exposure triggers an inflammatory response in the skin, which is much higher in men than in women, who have lower inflammation and melanocyte migration. Analysis of gene expression between men and women revealed that men’s higher skin inflammation in response to UVB was due to higher production of prostaglandins, a group of molecules produced in response to injuries and tissue damage. Literature research has shown that prostaglandins can stimulate melanocytes in various ways.

To confirm the effect of prostaglandin, the researchers exposed the mice’s white skin to UVB before injecting them with a prostaglandin solution. They observed that with prostaglandins, the migration of melanocytes from hair to skin was higher than with UVB alone, and became as high in women as in men.

“This gave us an opening to control the amount of melanocytes that enter the skin,” White said. “We were wondering what molecule can we rub on our skin to make this happen?”

Using UVB exposure with prostaglandin to treat vitiligo is particularly promising because a form of prostaglandin already exists on the market as a topical gel, used to speed up labor in men.

White filed a provisional patent for his therapeutic strategy, combining existing immunosuppressive drugs recommended to treat vitiligo with controlled UVB irradiation and prostaglandin supplementation – a three-pronged approach that showed the highest melanocyte migration in its mouse models.

As a next step, White wants to test possible topical applications that could penetrate deeper into the skin and refine the drug’s specificity by understanding “who the melanocytes are talking to” in the skin, he said.