Study Finds Topical Statin Aids Healing of Diabetic Foot Ulcers
An NIH-funded study by researchers at the University of Miami Miller School of Medicine has found that topical treatment with mevastatin will block two common healing inhibitors in diabetic foot ulcers, a life-threatening complication of diabetes mellitus with limited treatment options that often results in amputations.
Statins are cholesterol-reducing agents that target the cholesterol pathway and block the synthesis of the wound-healing inhibitors farnesyl pyrophosphate and cortisol, ligands for the glucocorticoid receptor. They may provide a new therapeutic option, report the researchers.
“We used a combination of in vivo porcine wound model, ex vivo human skin model and biopsies from diabetic foot ulcer patients to study mechanisms by which statins may accelerate wound healing,” said Marjana Tomic-Canic, Ph.D., professor of dermatology, vice chair of research, and director of the Wound Healing and Regenerative Medicine Research Program in the Department of Dermatology and Cutaneous Surgery, who was the lead researcher in the study.
“Our findings demonstrate a complex mechanism of action whereby topical statins modify glucocorticoid receptor ligands and stimulate endogenous cells to enter a healing mode. They also directly act on molecular inhibitors of healing in patients, such as c-Myc, both ex vivo and in vivo. Activation of c-Myc represents a hallmark of non-healing, chronic wounds that participates in hyper-proliferation of cells at the edge of the wound, exhausting the local population of epidermal stem cells. By modulating tissue glucocorticoids, topical statins can block activation of c-Myc and reverse inhibition of healing.”
The research findings were reported in an article, “Topical mevastatin promotes wound healing by inhibiting the transcription factor c-Myc via the glucocorticoid receptor and the long noncoding RNA Gas5,” published online by the Journal of Biological Chemistry, with Tomic-Canic as senior author. Additional Miller School co-investigators from the Department of Dermatology and Cutaneous Surgery were Robert S. Kirsner, M.D., Ph.D., Harvey Blank Professor and Chair, Irena Pastar, Ph.D., research assistant professor, and Stephen C. Davis, research professor. The lead author was Andrew P. Sawaya, a graduate student in the Department of Molecular and Cellular Pharmacology.
“Topical statins may have considerable therapeutic potential for patients suffering from chronic wounds that do not respond to standard treatments,” said Tomic-Canic. “Statins are a widely used class of drugs, particularly more recently in the diabetic population. Their safety profile and low cost make them excellent candidates for potential re-purposing as a therapeutic modality for patients with diabetic foot ulcers.”