Designed Host Defense Pepties for the Topical Treatment of Diabetic Foot Ulcers

Project Summary Abstract In addition to the pain and suffering they causethe fiscal cost of neuropathic diabetic foot ulcersDFUsis estimated to be over $billion yearEach year overlimb amputations are performed because current therapy is ineffectiveChronic infectionsoften residing in biofilms are implicated in the failure of DFUs to healRiptide Bioscience Inchas developed novel designed Host Defense PeptidesdHDPswith demonstrated bactericidal activity and the ability to eradicate bacteria in biofilmDesigned host defense peptides are derived from naturally occurring HDPs that are ubiquitous in nature and provide the first line of defense against invading pathogensIn this proposal three dHDPs with broad based efficacy will be evaluatedA splinted wound model on diabetic mice will be infected with bioluminescent strains of S aureus or P aeurginosaBactericidal activity will be followed in real time by an animal fluorescence imaging systemXenogen IVISRates of wound closure and revascularization will be assessedFrom these studies we will select a compound to undergo appropriate regulatory enabling studies with a Phase II SBIR that could lead to a commercially viable therapeutic for the treatment of diabetic foot ulcersPublic Health RelevanceNew treatments for diabetic foot ulcers are neededDesigned host defense peptides are rationally derived from naturally occurring antimicrobial peptidesThese novel therapeutic peptides are bactericidalpromote wound healing thereby preventing chronic pain and loss of function