Potential Tx for hypopigmentation?

Ampyrone increases pigmentation in a human 3D epidermal model, The top row shows visible epidermal darkening after treatment every other day with ampyrone for 21 days as compared to negative control. The bottom row shows magnification of epidermal cells revealing increased melanin synthesis in the ampyrone treated melanocytes as compared to negative control. Positive control is alpha-melanocyte stimulating hormone (αMSH) plus beta-fibroblast growth factor (βFGF). Photo by Dr. Jonathan Zippin

Researchers at Weill Cornell Medicine and the National Eye Institute report that a compound related to NSAIDs may offer a new way to treat disorders marked by too little skin pigment, including some forms of albinism. In a preclinical study published in JCI Insight, the team determined that ampyrone increased melanin production in human skin models without signs of toxicity in tests lasting as long as three weeks.

The findings are clinically notable because hypopigmentation disorders can carry risks beyond appearance, including heightened vulnerability to ultraviolet damage, vision problems, and psychosocial burden. The investigators said the work could eventually lead to a drug based on ampyrone for patients with conditions in which melanin production is impaired.

“Pharmacologic enhancement of human pigmentation represents a promising strategy for the treatment of diseases of hypopigmentation such as OCA [oculocutaneous albinism] by protecting skin, improving visual function and enhancing patient quality of life,” said Dr. Jonathan Zippin in a press release. He is an associate professor of dermatology at Weill Cornell Medicine and a dermatologist at New York-Presbyterian/Weill Cornell Medical Center. “Improving melanin pigmentation in the eyes of people with OCA could potentially help them with difficulties such as glare sensitivity and, if initiated early enough, with developing better vision,” added Dr. Brian Brooks of the National Eye Institute.

The study focused on tyrosinase, an enzyme central to melanin synthesis. Using a high-throughput screening platform, the researchers tested more than 34,000 compounds and identified ampyrone as the most promising activator, including against mutant forms of tyrosinase associated with albinism. The compound also accelerated melanin production in cell systems and in a three-dimensional skin model.

The researchers said ampyrone induced new melanin synthesis within one hour in their assay, underscoring both its potency and the usefulness of the new measurement method for pigment-related drug screening. They are now testing the compound as a lead for further drug development.