Accelerating Wound Closure in Patients with Diabetes

By: Almas Eftekhari

One of the most common complications associated with both type 1 and type 2 diabetes is delayed wound healing. If left untreated, wounds can lead to infection, amputation, and even death. In fact, diabetes is the leading cause of non-traumatic lower limb amputation in the United States. Despite a clear need, there are very few treatments available that are consistently effective in accelerating wound closure in people with diabetes.

Results from an ADA-funded study presented at the Association's 72nd Scientific Sessions introduced a novel treatment strategy that may significantly improve wound healing in these patients. Patricia J. McLaughlin, DEd,  and her research team from Pennsylvania State University School of Medicine have been exploring how to modulate the opioid growth factor – opioid growth factor receptor (OGF-OGFr) axis in the skin as a means to treat wounds.

Opioid receptors, particularly OGFr, and endogenous opioid peptides, regulate the replication of cells in the outer layers of skin, as well as in blood vessels.  As a cell and molecular biologist, Dr. McLaughlin has been carefully studying the roles of these pathways for nearly a decade. Thanks to ADA funding, she began investigating whether blockade of the opioid receptors at the wound site could enhance cell replication and accelerate wound closure in people with diabetes.

Dr. McLaughlin knew that naltrexone, a drug primarily used to treat alcohol and other drug addiction, potently blocks the activity of opioid receptors. She developed a naltrexone cream that can be applied locally to the skin, and tested it in a type 1 diabetes rat model of wound healing. Three times a day, the laboratory team applied the cream to the animals’ wounds and then studied the changes in the wound bed over the course of 20 days. The researchers were especially interested in observing signs of angiogenesis, or the physical development of new blood vessels at the wound site.

After just a few days, the scientists saw that the rats receiving naltrexone therapy had significantly faster wound healing than untreated rats. In fact, they exhibited similar healing to healthy rats without diabetes. Furthermore, while angiogenesis is usually inhibited in type 1 diabetes, the rats receiving naltrexone treatment showed dramatically elevated markers for angiogenesis. The researchers concluded that topical naltrexone therapy was very effective in accelerating full-thickness wound closures in the presence of type 1 diabetes, and that the development of blood vessels seems to be a target for the drug.

In future studies, the researchers will be taking a closer look at the pathways involved in blood vessel development and capillary density that naltrexone may be targeting. Dr. McLaughlin and her colleagues are also eager to test topical naltrexone therapy in clinical trials and are confident that the treatment will be as effective in humans as in animal models.  In the coming years, their work could potentially introduce an inexpensive and easy-to-use product for patients suffering from healing complications.

Dr. McLaughlin has recently published her findings in the journal Experimental Biology and Medicine.