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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43HL122078-01A1
Application #
8785946
Study Section
Special Emphasis Panel (ZRG1-CVRS-M (11))
Program Officer
Eu, Jerry Pc
Project Start
2014-08-18
Project End
2015-08-31
Budget Start
2014-08-18
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$224,823
Indirect Cost
Name
Sorrento Therapeutics, Inc.
Department
Type
DUNS #
832545805
City
San Diego
State
CA
Country
United States
Zip Code
92121