Development of a Novel Therapeutic Agent for Skin Fibrosis

Systemic sclerosis or scleroderma is an autoimmune rheumatic disease characterized by fibrosis of the skin and internal organs that has the highest case fatality among rheumatic diseases. The increased deposition of collagen and other extracellular matrix proteins in the tissues leads to impaired function of visceral organs and early death. Although several drugs such as recently approved nintedanib and tocilizumab may stabilize lung function in some scleroderma patients, none of those have a significant effect on skin fibrosis as measured by the modified Rodnan skin score, underscoring the need to develop new therapies for this potentially lethal disease. Small peptides are widely involved in multiple cellular events and play very important roles in various cell functions. Interest in peptides as potential drug candidates remains high. With advances in such fields as chemical synthesis and peptide formulation, peptide drugs - especially short synthetic and long-acting peptides - are quickly increasing in the global market. The advantages of small peptides as drugs include their high biological activity, high specificity, and low toxicity. FibroBiologics, LLC proposes to develop the novel peptide M10 as an efficacious antifibrotic therapeutic agent, with a lead indication for the treatment of patients who suffer from skin fibrosis associated with scleroderma. In Specific Aim 1, we will determine antifibrotic activity of M10 in primary skin fibroblasts isolated from scleroderma patients and evaluate an inhibitory effect of M10 on fibrogenic characteristics of scleroderma skin fibroblasts. In Specific Aim 2, we will define the efficacious dosing of M10 in two different animal models of dermal fibrosis: bleomycin-induced mouse model and FSP-driven TβR1CA mouse model. The successful completion of these two specific aims will provide important information about the feasibility of developing M10 as a novel therapeutic for skin fibrosis and will justify further studies focusing on gaining FDA clearance, scaling production, and a human clinical trial.