New anti-fibrotic drugs are needed to treat Idiopathic Pulmonary Fibrosis (IPF). IPF is a progressive, chronically debilitating clinical syndrome with unknown etiology and a terminal outcome. IPF symptoms include persistent cough, progressive severe shortness of breath and decreased exercise capacity. Up to 200,000 Americans suffer from this disease with expected survival limited to 3-5 years. There are currently no approved US drugs leaving lung transplantation as the only option to extend life. IPF is initially characterized by alveolar epithelial cell injury followed by epithelial-mesenchymal transition (EMT) and exaggerated fibroblast migration, activation and proliferation with extracellular matrix deposition and tissue remodeling. When a sufficient proportion of the IPF lung becomes scarred respiratory failure and comorbidities occur. WNT1- Inducible Signaling Protein-1 (WISP1;also known as CCN4) is an autocrine and paracrine extracellular stimulus for EMT. Studies have shown that: 1. WISP1 is induced in human lung cells by TGF-?;2. WISP1 is upregulated at the alveolar epithelial surface in IPF;3. WISP1 protein stimulates EMT and fibroblast ECM deposition in vitro;4. depletion of WISP1 with neutralizing antibodies attenuates bleomycin-induced pulmonary fibrosis in vivo. Currently, no IPF drugs are in development that target WISP1 or the WNT pathway. Together with our collaborators we have outlined experiments that will harness a powerful combination of antibody discovery, fibrotic pathway expertise and aerosol drug development to provide a solid basis for the discovery, evaluation and development of an anti-WISP1 immunotherapy for IPF treatment.
New anti-fibrotic drugs are needed to treat Idiopathic Pulmonary Fibrosis, a progressive, chronically debilitating disease of unknown origin, fatal outcome (3-5 years life expectancy) and no currently FDA- approved drugs. Up to 200,000 Americans suffer from this disease with expected survival limited to 3-5 years. Together with our collaborators, Sorrento Therapeutics, Inc. has designed experiments that will discover, evaluate and develop of a new and desperately needed therapy for IPF treatment.