Public Abstract. Acne vulgaris is a chronic inflammatory skin disorder affecting more than 80% of all adolescents and young adults worldwide. Acne causes a substantial cutaneous and psychologic disease burden, often creating crippling effects in patients? self?esteem and socialization. Acne management results in high monetary and physician use demands in the United States, accounting for more than 5 million doctor visits each year and resulting in costs in excess of $2.5 billion. Antibiotic therapy has been integral to acne management however the widespread, and often permissive, use of antibiotics has led to the emergence of resistant P. acnes bacteria. Moreover, biofilm formation by P. acnes, which comprise sophisticated colonies of microorganisms encased in a resilient dense extracellular matrix increases its resistance against antimicrobial agents. Biofilms are. Despite the critical need for new antibiotics with novel modes of action, the development of antibacterial agents has drastically declined in recent years. Designed antimicrobial peptides (dAMPs), created by Riptide Bioscience Inc, are chemically derived from naturally occurring AMPs which are ubiquitous in nature and provide the first line of defense against invading pathogens. dAMPs have a reduced likelihood of spurring bacterial resistance, exhibit potent antimicrobial activity against the Gram-positive P. acnes pathogen and have known anti-inflammatory properties. Based on the initial encouraging antimicrobial results observed in planktonic isolates and biofilm cultures for P. acnes and demonstrated in vivo antibacterial and anti-inflammatory activity, we propose that these novel peptides may treat acne infections while exhibiting less susceptibility to bacterial resistance. In this proposed investigation, the in vitro antibacterial activity of dAMPs against P. acnes isolates and biofilm will be evaluated, dAMP-mediated P. acnes bactericidal kinetics in the absence and presence of sebum will be assessed, the cytotoxicity of dAMPs on human keratinocytes will be determined and the antimicrobial efficacy of the lead peptides in ameliorating infection in an inflammatory P. acnes murine model will be determined. If successful, a product candidate will be selected to be advanced, via a SBIR grant-funded Phase II study, to FDA-required preclinical studies with the goal of developing a commercially viable therapy for the treatment of infectious acne vulgaris.
The alarming increase in drug resistant acne infections has generated an urgent need for new antibacterial agents with potent activity and novel modes of action. Designed antimicrobial peptides were rationally derived from innate broad spectrum antimicrobial peptides by Riptide Bioscience Inc. Upon receipt of this Phase I SBIR grant, Riptide Bioscience Inc will further advance the development of an efficacious microbiocidal with potent antimicrobial and anti-biofilm activity, with a reduced likelihood of developing bacterial resistance, for the treatment of infectious acne vulgaris.
