In the paper, the authors note that prior research has implicated dysregulation of the skin’s rennin-angiotensin system (RAS) in abnormal wound healing in both older adults and in diabetic patients. This led them to investigate the effects of topical reformulations of the angiotensin type 1 receptor blockers (ARB) losartan and valsartan, and the angiotensin-converting enzyme (ACE) inhibitor captopril on wound healing in murine and porcine models.
“The FDA has not issued any new drug approval for wound healing in the past 10 years,” said Dr. Peter Abadir, associate professor of medicine at the Johns Hopkins University School of Medicine and the paper’s first author, in a press release. “Using medicines that have been available for more than two decades, we think we have shown that this class of medicines holds great promise in effectively healing chronic wounds that are prevalent in diabetic and aged patients.”
Investigators found that in murine models of chronic wounds in older and diabetic subjects, valsartan was more effective in accelerating wound healing than losartan, without any significant difference in healing time between valsartan doses. Overall, valsartan 1% had the greatest impact on total closure compared with the other agents. Losartan 10% led to the worst wound healing, which Dr. Abadir said may be attributed to toxicity of the formulation.
In the final results, half of all mice that received valsartan 1% achieved complete wound healing, compared to only 10% of the mice given the placebo.
The findings were replicated in a porcine model of diabetic chronic wounds. Compared with pigs in the placebo group, wounds that received valsartan 1% healed much more quickly, and all 12 wounds were closed by day 50, compared with none of the placebo-treated wounds, the researchers write.
There was little evidence of systemic absorption as well, with a low concentration (1 to 50 nanomoles) of valsartan detected in the pigs’ blood near the beginning of treatment, and none was detected later in the treatment course.
Pigs treated with valsartan also had a thicker epidermal layer and dermal collagen layer, as well as a more organized collagen fibre arrangement, which the authors say indicate valsartan 1% application leads to stronger healing skin.
“Our strategy for specifically targeting the biology that underlies chronic wounds in diabetics and older adults differs greatly from other approaches to wound care thus far. The topical gel likely enables a cascade of positive biological effects that facilitates and accelerates chronic wound healing,” said the paper’s senior author Dr. Jeremy Walston, professor of medicine at Johns Hopkins University School of Medicine, in the release.
“Now that we’ve proven efficacy in animals, we’re moving on to the next stage of FDA-required testing in humans. Hopefully, this medication will be available for public use in a few years, if further research bears out our results,” said Dr. Walston. Dr. Walston and colleagues envision that the medication could one day also be used to treat scars, wrinkles and other skin problems.