New research on inducing closure of chronic wounds could aid in healing diabetic foot ulcers, say the investigators who have identified a new way to induce tissue growth and regeneration.
In a paper published in Nature Chemical Biology (March 15, 2021), the researchers report the discovery of a small molecule, which they call PY-60. In vitro, this molecule activates transcriptional activity of Yes-associated protein 1 (YAP), which they say regulates organ size and the regenerative responses of certain tissues. YAP is regulated via a molecular pathway called Hippo, which the authors of the paper note is often a target of cancer drugs due to its ability to influence cell growth.
Topical application of PY-60 in mouse wound models also resulted in an expansion of epidermal keratinocytes.
“We developed a way to activate multiple aspects of wound healing using a small-molecule drug that can be applied topically, without affecting other tissues,” said the paper's senior author, Michael Bollong, PhD, in a press release. “Essentially, we were able to trick the cells into proliferating and closing the wound, restoring the outer layers of skin.”
Dr. Bollong is an assistant professor at Scripps Research, a nonprofit U.S. medical research facility in La Jolla, Calif.
Through their research, the scientists found a previously unknown player in the Hippo pathway. This was a protein that works with YAP to communicate cell density, halting cell growth when an organ or other tissue reaches a certain concentration. But by targeting this protein with PY-60, tissue cells return to production mode.
“We found the results of the study to be incredibly compelling,” said Dr. Bollong. “We hope this regenerative approach can eventually be added on to existing standards of care for diabetic foot ulcers.”
In addition to the potential for treating chronic wounds, Dr. Bollong said that this approach might lead to new regenerative therapies for heart disease, liver conditions, and inflammatory bowel disease.
“We believe the future of this type of regenerative therapy is incredibly bright,” he said.
The near-term focus for the group is diabetic foot ulcers, according to the release. Dr. Bollong notes that the only existing regenerative therapy for these wounds was developed more than two decades ago and has limited efficacy. They hope to begin clinical trials within the next year.