A novel anti-scar peptide for cutaneous wound repair

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 DESCRIPTION (provided by applicant): Cutaneous fibrosis (scarring) affects up to 100 million patients per year as a result of 55 million elective operations and 25 million operations after trauma. Besides concerns of cosmesis, scarring can have significant functional sequelae. Overall, scar prevention strategies for skin are minimally effective. Currently available techniques focus on reducing the appearance of already formed scars (e.g., silicone sheeting, topical ointments, lasers). Other scar reduction strategies that target the scar formation process such as steroids and radiation can have undesirable side effects. With these substantial limitations, there remains a pressing need for the development of alternative therapies for the prevention of cutaneous scarring. Through a sustained, 14-year research effort examining models of fetal wound healing, we have identified fibromodulin (FMOD) as a novel molecule required for fetal scarless skin repair. FMOD protein decreases scarring and improves extracellular matrix (ECM) organization in adult wounds. These findings have been confirmed across multiple mammalian species. As a technological innovation, we have developed a 40 amino acid FMOD peptide sequence, F06-C40, which can undergo rapid and inexpensive production and is similar to the 376 amino acid full FMOD protein in its anti-fibrotic effects. Because porcine skin is the closest animal skin equivalent to that of humans and is the Food and Drug Administration (FDA)- preferred model for testing wound healing products, we have established the optimal dose and regimen of F06- C40 (F06-C40OPT) that effectively improves gross visual appearance, reduces scar size, and maintains wound tensile in a Yorkshire pig primary wound closure model simulating human scar revision surgery. In addition, we have confirmed that F06-C40OPT has the same effects in a red Duroc pig model simulating human hypertrophic scarring, and we are ready to apply it to Investigational New Drug (IND)-enabling studies. Moreover, we have demonstrated that F06-C40 does not have in vivo adverse local effects in mice, rats, and pigs - notably, up to 50 mg/ml with 0.3 ml was applied for 1.5 cm (10 mg/cm) of wound in the porcine models. Furthermore, we have also proved that no significant systemic toxicity is observed in rats with up to 100 mg/kg F06-C40 [which can be converted to a 16 mg/kg human equivalent dose (HED); for a 60 kg male, this dose can be translated to approximately a 960 mg total dose, enough to treat a 960 cm linear scar. This far exceeds the size of typical scars and the anticipated amount of F06-C40 required for treatment (e.g. 1 mg per every linear cm of scar)]. Thus, we have accomplished all aims proposed in our previous SHIFT-SBIR Phase I award (1 R43 AR064126- 01). The goal of the current SBIR Phase II application is to perform critical IND-enabling studies for first-in-man F06-C40 clinical trials an to allow bench to bedside translation of FMOD peptide-based therapy to prophylactically reduce cutaneous scar formation.