Bacterial keratitis, due to its potential to cause irreversible blindness, requires prompt intervention. In the United States there are approximately 30,000 patients annually, with contact lens wear being the prime risk factor. Bacterial keratitis i presently treated with antibiotics however innovation in antimicrobial agents and treatment is needed due to the rapid emergence of bacterial resistance and resilience due to biofilm formation. Designed host defense peptides (dHDPs) are derived from naturally occurring HDPs which are ubiquitous in nature and provide the first line of defense against invading pathogens. Aero-Dap LLC has developed novel dHDPs with potent antibacterial activity which may also promote wound healing while concurrently reducing scarring and inflammation and thereby prevent potential blindness in patients with bacterial keratitis. In this proposal, the in vitro cytotoxicity and anti-inflammatory effects of the peptides will be evaluated on corneal epithelial cells and fibroblast cells. Wound healing will be assessed in an in vitro model prior to the lead peptide being evaluated in an in vivo corneal wound model. The antimicrobial efficacy of the lead peptide will be assessed in a keratitis model. If proved successful the compound will undergo the appropriate regulatory- enabling studies with a SBIR grant-funded Phase II study that could lead to a commercially viable therapeutic agent for the treatment of bacterial keratitis
New antibiotics for the eye are needed as current antibiotic therapies are showing decreased efficacy due to bacterial resistance. Designed host defense peptides were rationally derived from naturally occurring antimicrobial peptides by Aero-Dap LLC. These novel therapeutic peptides have exhibited potential to directly kill microbes while promoting wound healing thereby preventing corneal damage and blindness.
|Clemens, L Edward; Jaynes, Jesse; Lim, Edward et al. (2017) Designed Host Defense Peptides for the Treatment of Bacterial Keratitis. Invest Ophthalmol Vis Sci 58:6273-6281|