A research team at Stanford (Calif.) University School of Medicine has developed a drug delivered through a skin patch that not only helps foot wounds heal better, but also prevents those wounds from recurring, according to preliminary study results.
The team presented their results in October at the American College of Surgeons Annual Clinical Congress in San Francisco.
Amputations are one of the most serious complications of diabetes. About 29.1 million Americans are living with diabetes. Among adults who have lower-limb amputations unrelated to trauma, about 60% have been diagnosed with diabetes, according to the American Diabetes Association.
Foot ulcers are a major reason why people with diabetes need foot amputations, according to Geoffrey Gurtner, MD, FACS, the Johnson & Johnson Professor of Surgery and associate chairman of surgery for research at Stanford University School of Medicine. However, even after the operation, many patients fare worse.
Its not just having your leg surgically removed, study co-author Gurtner said in a news release. An amputation sends these patients into a downward spiral where they are not active. Then, all the other health issues that accompany inactivity come into play. A diabetic patient who undergoes an amputation has a 50% five-year mortality, which is worse than breast cancer or Hodgkins disease.
Foot ulcers are particularly dangerous for people with diabetes because the impaired blood flow prevents the wound from healing properly, Gurtner said.
You can clear out blockages of the big blood vessels with stents or bypasses, but that treatment only solves half the problem, he said in the release.
In addition to blocked blood vessels, the blood sugar toxicity in people with diabetes impairs a protein, called hypoxia inducible factor-1 alpha, or HIF-1α. This protein turns on the genes that help form new networks of small blood vessels needed to heal damaged tissue.
At the microcirculation level, the small capillaries are the final distribution for blood, oxygen and nutrients to tissue, Gurtner said in the release.
Based on that mechanism, Gurtner and his colleagues developed a drug that increases the protein HIF-1α in diabetes patients. The drugs main ingredient is deferoxamine, a medication that has been available for more than 60 years, but the drugs molecules are too large to penetrate the skin adequately.
If you just put it on the skin, it wont get through, Gurtner said in the release. So, we needed to develop a transdermal patch to serve as the drugs delivery tool.
The Stanford research team tested both methods using a human skin apparatus. Their results showed the patch had several advantages compared with a topical solution. The wound healed 14 days faster, and the patch also boosted the quality of the wound healing by improving the damaged skins collagen levels. This quality also could help prevent repeat ulcers and possibly even prevent initial ulcers, the researchers said. Patients who have diabetic foot ulcers have a 50% chance of it re-ulcerating within a year, Gurtner said.
We have lots of diagnostic modalities to tell patients their feet are at risk for a wound by how much oxygen is getting to the skin, blood flow and which areas are at risk, he said in the release. But, when we find that theres low oxygen or delivery of blood, theres not much we can do except tell the person to take better care of their feet. This drug could actually change the biology of diabetic patients.
The next step to bring the drug to market is a clinical trial testing the drug with diabetes patients who are at risk for foot ulcers.
This study was supported by the National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases) and the Harrington Discovery Institute.