Safety and efficacy testing of novel anti-scar peptide vs corticosteroid for scar

DESCRIPTION provided by applicant Cutaneous fibrosis scarring affects up to million patients per year in developed countries Scarring especially hypertrophic scarring can have significant morphologic and functional sequelae requiring multiple revision surgeries to restore function and improve appearance The incidence of hypertrophic scarring varies following surgery and can be up to following burn injury Current methods for the treatment of hypertrophic scars are minimally effective or have undesirable side effects Steroids e g Triamcinolone are FDA approved for intralesional injection into hypertrophic scars but have significant side effects including granulomas and skin atrophy that leads to reduced wound strength Moreover many hypertrophic scars are refractory to steroids or other non surgical therapies and require revision surgery However revision surgery for hypertrophic scar also has a high rate of recurrence Through a sustained year research effort examining models of fetal wound healing we have identified fibromodulin FMOD as a novel molecule required for fetal scarless skin repair In a technological innovation we have identified a amino acid peptide sequence F C which has similar anti fibrotic effects as the amino acid full FMOD protein Excitingly we have demonstrated using a pig model of human hypertrophic scarring that both FMOD protein and its peptide derivative F C can significantly reduce scar formation In this proposal we will test the hypothesis that F C is more efficacious than corticosteroids for reduction of hypertrophic scar formation AIM Months Optimize F C for scar prevention in pig hypertrophic scar models and compare it with corticosteroids AIM will optimize the dose of F C for hypertrophic scar reduction and compare the optimized formulation with corticosteroid injection Two wound models in Red Duroc pigs a porcine breed that most closely simulates human hypertrophic scarring will be used Primary outcome measures will include improved gross visual appearance without a reduction in wound tensile strength AIM Months Accomplish initial safety studies for F C first in man studies AIM will focus on accomplishing key studies required by the FDA at the pre IND meeting for F C Studies will consist of preliminary genotoxicity and intravenous toxicology studies in rats Hypertrophic scars cause significant functional and cosmetic impairment This SHIFT SBIR proposal focuses on optimizing the treatment regimen for F C proving its superior efficacy compared with current strategies for scar reduction and verifying its initial product safety PUBLIC HEALTH RELEVANCE Costs of excessive cutaneous scarring and other wound healing complications approach billion dollars per annum and up to million patients acquire scars per year In addition hypertrophic scarring is especially prevalent in minority populations while pathologic scarring affects numerous other organ systems such as liver lung and kidney in often fatal disease processes This project seeks to develop effective novel peptide based treatment to reduce hypertrophic scarring