Drug identified that rescues healing response in chronic wounds

Chronic wounds are wounds that fail to heal properly and can remain open for months or even years. They often occur in people with other health conditions such as diabetes, obesity, or advanced age. Common types include venous leg ulcers, diabetic foot ulcers and pressure sores.

Instead of moving through the normal healing stages, these wounds become trapped in a cycle of persistent inflammation. This can lead to serious complications including infection, amputation, sepsis, and even death. Treating chronic wounds is a growing global challenge, costing the UK’s National Health Service around £8 billion each year and affecting millions of people worldwide.

Activation of protein called the MC1R receptor improves wound healing

IRR researchers from the Cash lab focussed on a receptor called MC1R, which plays an important role in controlling inflammation. Receptors are special proteins found inside or on the surface of cells, and once bound to signaling molecules, initiates a specific effect within the cell.

This study develops the first preclinical model of human chronic wounds and finds that applying a topical drug that activates MC1R improved healing in chronic wounds of mice. Mice without a functioning MC1R also developed more severe wounds. 

The same treatment also accelerated normal wound healing by improving blood vessel growth, reducing harmful inflammation from immune cells and reducing scarring.

Dysregulated molecular pathway is a feature of chronic wounds

They also found that the naturally occurring signalling molecule for MC1R (called POMC) is less abundant in human pressure ulcers, venous leg ulcers and diabetic ulcers. Since this pathway is important in controlling inflammation, lack of signalling molecule indicates lack of activation of the receptor. 

Finding this in several types of chronic wounds suggests that dysregulation of this pathway may be a key feature of non-healing wounds and actually contribute to failed repair. 

Benefits to patients

MC1R activator medications such as afamelanotide and dersimelagon have already shown favourable safety profiles in clinical trials for other conditions. 

This supports their potential to be developed as a topical therapy for chronic wounds - applied during routine dressing changes to promote healing while minimising effects on the rest of the body.

This work was funded by Wellcome.

Read the full paper in The Proceedings of the National Academy of Sciences (PNAS)

Cash research group