Development of Soluble Small Molecule Anti-Fibrotics for the Treatment of Fibrosis in the Orphan Disease Systemic Scleroderma
Carol M. Artlett, PhD, Associate Professor of Microbiology and Immunology at Drexel University’s College of Medicine.
Sandhya Kortagere, PhD, Associate Professor of Microbiology and Immunology at Drexel University.
John Varga, MD, Clinical Partner
Systemic scleroderma (SSc) is a fibrotic disease involving the vasculature, skin, and internal organs. It is a rare/orphan disease affecting ~150,000 patients in the U.S. and about 10,000 die annually of this disease. It is one of the most lethal of the rheumatic diseases and is associated with a significant loss of health related quality of life. Patients die of cardiac or pulmonary failure due to fibrosis. There are currently no therapeutics that control fibrosis in this disease. Recently, we found that fibrosis is dependent on IL-1 and hypothesized that by blocking the IL-1 receptor (IL-1R) we would abrogate fibrosis. We identified three small soluble molecules with an IC50 of 1 nM that antagonize the IL-1R. Validation studies demonstrate that our lead compounds specifically block the excessive production of collagen by IL-1α and IL-1β and abrogate fibrosis in patient derived fibrotic cells. Biological drugs that target IL-1 have been successful in treating several IL-1 mediated diseases but are not approved for use in SSc. We have developed novel orally available small soluble molecule therapeutics that could be used as anti-fibrotics in the disease SSc.