Anti-scar peptide for cleft lip repair

DESCRIPTION provided by applicant Cleft lip and palate CLP is the most common craniofacial congenital anomaly in the US Since CLP can cause severe developmental functional aesthetic and psychological difficulties if not corrected it is the most frequently reported birth defect requiring surgery Unfortunately hypertrophic scar HS formation is a common complication of cleft lip repair surgery according to various studies and often requires multiple surgical revisions HS management in CLP repair is significantly more challenging than other scars due to lack of tissue cleft excessive tension in the repaire cleft due to missing tissue action of the perioral muscles and head growth and higher expectations for aesthetics Current treatments such as corticosteroids have undesirable side effects such as reduced wound strength and skin atrophy while radiation carries a risk of future malignancy Therefore there is a pressing need for alternative therapies to reduce HS formation especially in CLP repair We previously identified fibromodulin FMOD as being critical for fetal scarless skin repair Remarkably FMOD protein application to adult wounds can decrease scarring without reducing wound tensile strength in multiple mammalian species including mouse rat and pig In a technological innovation we have developed a synthetic amino acid FMOD peptide sequence F C that exhibits similar efficacy as the amino acid FMOD whole protein F C can be produced much more rapidly inexpensively and with higher purity than FMOD protein Like FMOD F C significantly reduced scar without compromising wound strength in two separate pig models Yorkshire pigs simulating normal human scar and red Duroc Pigs more closely simulating human HS Importantly at our recent pre Investigational New Drug IND meeting the Food and Drug Administration FDA clearly outlined the required safety studies before first in man F C clinical trials The goal of this Fast Track SBIR proposal is to perform these critical IND enabling studies to accelerate bench to bedside translation of FMOD peptide based therapy to minimize HS formation in CLP patients The Phase I Milestone will be to establish an optimized F C dose andquot testable product formulationandquot demonstrating significant efficacy compared with control in improved gross visual appearance scar size reduction and wound tensile strength maintenance With the andquot testable product formulationandquot in hand the Phase II Milestones will be to complete F C mode of action and FDA required safety studies establish quality control assays for F C and submit a well supported IND application that is accepted by the FDA to initiate Clinical Phase I studies Overall this proposal will accomplish key regulatory Chemistry Manufacturing Controls CMC and business objectives to expedite F C product commercialization If successful F C based therapy can significantly improve the quality of life of CLP patients suffering from HS and patients with HS from burns surgery or other trauma PUBLIC HEALTH RELEVANCE Cleft lip and palate is the most common birth defect of the head occurring at a rate of per live births in the US Cleft lips are typically repaired during infancy but hypertrophic or excessive scar formation is a common complication surgery This excessive scarring often tethers or retards the growth of bone and soft tissues in the upper jaw lip and leads to the need for extensive surgeries to correct both the bone and soft tissue deformities This project seeks to develop an effective novel peptide based treatment to reduce scarring and improve the quality of life of cleft lip and palate patients suffering from excessive scar formation