Scientists discover Novel Regenrative Treatment Path for Diabetic foot ulcer

"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," Bollong says. "Essentially, we were able to trick the cells into proliferating and closing the wound, restoring the outer layers of skin."

Bollong's group along with the laboratory of Scripps Research President and CEO Peter Schultz, PhD, and drug discovery teams at Calibr, screened more than 800,000 molecules to find one that stimulated key regenerative pathways.

They discovered the novel molecule PY-60, which robustly activates YAP transcriptional activity in vitro and promotes YAP-dependent expansion of epidermal keratinocytes in the mouse following topical drug administration.

Upon chemical proteomics, they found a relevant target of PY-60 to be annexin A2 (ANXA2), a protein that directly associates with YAP at the cell membrane in response to increased cell density.

Beyond treating chronic wounds, Bollong says the approach may lead to new regenerative therapies for heart disease, liver conditions and inflammatory bowel disease, or IBD. "We believe the future of this type of regenerative therapy is incredibly bright," Bollong says.

They found that treatment with PY-60 liberates ANXA2 from the membrane which ultimately promotes a phosphatase-bound, nonphosphorylated and transcriptionally active form of YAP.

The authors concluded, "This work reveals ANXA2 as a previously undescribed, druggable component of the Hippo pathway and suggests a mechanistic rationale to promote regenerative repair in disease."

"We found the results of the study to be incredibly compelling," Bollong added. "We hope this regenerative approach can eventually be added on to existing standards of care for diabetic foot ulcers."

For further information:

https://www.nature.com/articles/s41589-021-00755-0