(WHS-P4.04) ELU42, A SMALL MOLECULE WNT SIGNALING INHIBITOR, SIGNIFICANTLY ACCELERATES WOUND CLOSURE AND PROMOTES REGENERATIVE REPAIR FOLLOWING CUTANEOUS AND THIRD-DEGREE BURN INJURY IN YORKSHIRE PIGS
Friday, May 17, 2024
10:30 AM – 11:30 AM East Coast USA Time
Background: The canonical WNT signaling pathway is quiescent in many mammalian organs and becomes activated in response to injury. WNT signaling promotes fibrotic wound healing (including scarring) following acute cutaneous injury. Topical “spray-on” application of a proprietary WNT signaling inhibitor accelerated wound closure and promoted regenerative cutaneous repair in acute and third-degree burn wounds.
Methods: In this study, we utilized two (2) porcine models to analyze wound repair. Six (6) full-thickness 3 x 3 cm2 acute and ten (10) third-degree burn excisional wounds were created on the backs of Yorkshire pigs. ELU42, a novel, potent, aqueously soluble, topical “spray-on” small molecule WNT signaling inhibitor, was applied three (3) days a week (Mon, Wed, Fri; 200mL) up to Day 30. The animals were allowed to heal for another 30 days before being sacrificed at Day 60. Histopathological analyses were performed on excised tissues.
Results: In full-thickness acute and third-degree excisional wounds, topical application of the novel small molecule WNT signaling inhibitor, ELU42, significantly promoted wound closure, and also promoted regeneration of tissue, as evidenced by the presence of restored skin architecture with adnexal structures and restoration of well-organized granulation tissue. A statistically significant increase in rete peg formation at the dermal–epidermal junction was also identified. Significance calculations were performed using a two-way Analysis of Variances (ANOVA) using the Prism10 software (Graph-pad prism). P<0.05 was considered significant.
Conclusions: Until now, studies using small molecule WNT signaling inhibitors were limited for therapeutic usage due to their poor aqueous solubility. We have created ELU42, a water-soluble small molecule WNT signaling inhibitor, in spray-on form. It is a non-toxic potential drug, and does not require a sterile environment when applying to traumatic soft tissue (acute) wounds and third-degree burns. Our study presents a stable, potent, bioavailable, small molecule WNT signaling inhibitor that has strong pharmacological potential for use as a therapeutic for the regenerative repair of cutaneous wounds.