Topical Statin Continues to Show Promise for Healing Chronic Skin Wounds

Statins are well-known medications that can help people lower high cholesterol levels. Now a new study shows a topical formulation of mevastatin in development could help heal chronic skin wounds.

Standing, from left, Joshua D. Fox, M.D., Irena Pastar, Ph.D., Lisa Liang, Ph.D., Olivera Stojadinovic, M.D., Marjana Tomic-Canic, Ph.D., Rivka C. Stone, M.D., Ph.D., and Ashley Rosa, M.D. Kneeling, from left, Ivan Jozic, Ph.D., Horacio A. Ramirez, Ph.D., and Andrew P. Sawaya, Ph.D.

University of Miami Miller School of Medicine researchers report the novel discovery in the journal JCI Insight.

The results of the NIH-funded study demonstrate “the therapeutic potential of using already FDA-approved statins as a topical treatment for chronic wounds that are otherwise non-responsive to standard treatment options,” said senior author Marjana Tomic-Canic, Ph.D., professor, vice chair of research and William H. Eaglstein Chair in Wound Healing in the Dr Phillip Frost Department of Dermatology and Cutaneous Surgery at the Miller School.

The current work builds on earlier findings. Previously, the same research team showed mevastatin boosted wound closure in pig wound models and in samples of human skin. This time, along with lead author Andrew P. Sawaya, Ph.D., Dr. Tomic-Canic and colleagues evaluated how the statin accomplishes this beneficial effect.

Topical mevastatin effectively targets caveolin-1, a membrane protein in skin cells that prevents wound healing stimulatory signals to facilitate cell migration and wound closure. Mevastatin reverses this caveolin-1 block, allowing epidermal growth factor receptor to function. In turn, epidermal growth factor can do its job — stimulate skin cells to migrate across a wound and complete the healing process to restore the skin barrier.

How mevastatin provides this beneficial effect was verified in a genomic analysis. Using human keratinocytes — the predominant cell type in the outer layer of the skin — the investigators confirmed the statin can turn on genes that promote skin cell migration across a wound. At the same time, mevastatin can turn off genes associated with hyperproliferation, or excessive cell production. This is important because in patients with chronic wounds, despite a high production of new skin cells, healing does not occur because the cells cannot move across the ulcer to close it.

The accuracy with which mevastatin turns off one action while promoting another “is important because this is precisely what is needed in patients,” Dr. Tomic-Canic said.

Although the current study focused on non-healing diabetic foot ulcers, the results could someday lead to effective treatments for other chronic, non-healing wounds as well. Dr. Tomic-Canic said,

“From a biological standpoint, this is the first evidence of selective targeting of only one EGF function, which provides a unique opportunity for therapeutic interventions.”

Going forward, Dr. Tomic-Canic and colleagues plan to continue evaluating mechanisms by which such selective targeting occurs. They also want to further develop topical mevastatin with the ultimate goal of translating their research findings into treating patients in the clinic.

Additional Miller School faculty contributing to the study include Ivan Jozic, Ph.D., Rivka C. Stone, M.D., Ph.D., Irena Pastar, Ph.D., and Robert S. Kirsner, M.D., Ph.D.

Tags: Caveolin-1, diabetic foot ulcers, Marjana Tomic-Canic, mevastatin, topical statins, wound healing