MC1R & Red Hair: New Treatment Hope?

Chronic wounds (CWs), like diabetic ulcers or pressure sores, are a major health care challenge, especially in the elderly. These wounds, marked by persistent inflammation, often lead to infection and poor patient outcomes. While inflammation is a key part of the wound healing process, the inflammation exhibited by chronic wounds tends to last longer, inhibiting other healing processes.

A group of researchers at the University of Edinburgh have identified a common genetic feature associated with chronic wounds—and may have found a way to reverse some of the inflammation and accelerate healing for many people suffering from these wounds.

Their work, published in the Proceedings of the National Academy of Sciencesdetails how the MC1R gene—normally responsible for pigmentation and UV protection—also affects wound healing.

MC1R dysfunction in redheads

Proresolving mediators and their pathways help resolve inflammation and promote tissue repair in the body. Knowing this, the researchers analyzed several proresolving pathways to determine their role in chronic wound healing. They conducted analysis of single-cell RNA sequencing data from human wounds to identify pathway dysregulation.

The team found that dysregulation of the POMC–MC1R axis is a common feature in human chronic wounds, such as diabetic, venous or pressure ulcers. This occurs when the MC1R protein is inactivated or partially inactivated. And because the same protein is responsible for pigmentation in hair color, whether or not the protein is active tends to go hand-in-hand with hair color.

Redheads face impaired wound healing: MC1R dysregulation to blame, but a new treatment might help” title=”Dysregulated POMC-MC1R axis in human chronic wounds. Credit: Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2503308122″/>

People with brown or black hair generally have normal functioning MC1R variants, keeping it active. However, redheads have variants that completely switch off MC1R or make it only partially active. Those with blond hair usually have at least some level of MC1R activity.

The researchers went further by testing how wounds on older mice with either red or black fur healed. They say that 95.0% of the red-haired mice’s wounds (those with impaired MC1R) retained a scab after seven days, in comparison to 68.8% of the dark-haired mice’s wounds.

The red-haired mice also showed delayed reepithelialization and increased neutrophil extracellular traps (NETs), which are web-like structures of DNA, histones, and proteins that trap and kill pathogens in wounds.

“We find that lack of functional MC1R profoundly impaired healing, with significantly delayed wound closure detectable at 1, 7, 10, and 14 d postinjury,” the study authors write.

Topical treatment shows impressive benefits—for some

The researchers then decided to test out a potential remedy in the form of a topical MC1R agonist treatment. They applied the treatment on half of their group of wounded mice and a gel without the MC1R agonist on the other half after debriding their wounds.

They say the application of the MC1R-selective agonist restored healing, reduced exudate, improved blood vessel formation and decreased NETs. It even unexpectedly reduced scarring in acute wounds.

“MC1R-Ag treatment following debridement rescued the healing response, with an additional 33% reduction in wound area over debridement alone by 14 DPI, rising to 68% at 21 DPI,” the study authors write.

The caveat is that this treatment will only work for those with at least partially functional MC1R proteins. If the gene is completely switched off, the treatment can’t work. For this reason, the treatment part of the experiment only used mice with dark fur.

Still, the treatment shows a lot of promise for many individuals with chronic wounds. Although the mouse models used in these experiments were designed to resemble human wound function as much as possible, the models likely do not fully replicate the complexity of human chronic wounds.

Human trials for the treatment, however, are on the horizon. The team is hopeful, since MC1R agonists have been used for other treatments and demonstrate favorable safety profiles in clinical trials.

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