Treating drug-resistant infections of burn wounds with an optimized antimicrobial peptide

Project Summary/Abstract Burn wounds result in 400,000 emergency department visits in the U.S. each year. Around 10% of these patients require hospitalization where they are particularly susceptible to multi-drug resistant nosocomial (healthcare-associated) infections due to the loss of skin barrier function and the extended hospital stays, which are often required for wound healing. None of the currently available treatments meets all the desired properties of a topical antibiotic for burn wound care. In response to this clinical gap, the long term goal of the proposed project is to develop a universal antibiotic solution that is effective against all drug-resistant bacteria commonly found in burn wounds, does not cause new resistance, does not inhibit wound healing and which can be applied on all skin surfaces without adverse effects. Gavia BIO, LLC will develop the antimicrobial peptide DGL13K as a novel topical treatment for burn wound infections. This unique, patented peptide is effective against all tested bacterial pathogens, including biofilms and drug-resistant strains. DGL13K reduces infection in a human skin explant model and animal models without causing topical or systemic toxicity. DGL13K does not inhibit wound healing. Thus, DGL13K meets the desired properties of a topical burn wound treatment and fills an urgent need that is not met by currently available treatments. The goal of this Phase I project is to progress the preclinical development of DGL13K by demonstrating that topical formulations are a safe and effective broad-spectrum treatment for burn wound infections in vivo. Three specific aims are proposed to reach this goal. Research in Aim 1 will test additional species, and expand the library of bacteria and drug-resistant strains that are found in burn wounds and can be treated with DGL13K. Aim 2 will test topical formulations of DGL13K in a porcine burn wound infection model. The peptide will be tested in a soluble formulation and a self-assembling hydrogel formulation to determine if DGL13K affects bacterial load and time to closure for burn wounds in the porcine model. Research in Aim 3A will determine if mice develop hypersensitivity to DGL13K after repeated wound applications, while aim 3B will determine if DGL13K is found in circulation after repeated wound applications. The expected outcome of this work will expand the safety profile for DGL13K by including safety in a burn wound model in preparation for clinical application of the peptide. Gavia BIO will develop DGL13K in collaboration with researchers at the University of Minnesota. The initial focus is on serious burn wounds, which are mainly treated in regional burn centers that present a focused target market.