Respiratory, Cardiovascular, Gastroenterology, Nephrology
Thy-1 Mimicry as a Therapeutic Strategy for Pulmonary Fibrosis
2022 Harrington Scholar-Innovator
Progressive pulmonary fibrosis (PPF) is a debilitating, often-fatal scarring process complicating many acute and chronic lung diseases, including COVID-19. Existing FDA-approved drugs only slow the progression of PPF. No curative therapy exists.
Dr. Hagood, a pediatric pulmonologist, and Ronit Freeman, PhD, an associate professor of applied physical sciences at UNC, have developed molecular mimics for a cell surface matrix-interacting glycoprotein, Thy-1. The mimics function as fibrosis suppressors via modulation of profibrotic signaling molecules at the surface of activated fibroblasts. In vitro, the mimics have shown the ability to restore homeostatic functions of profibrotic human lung fibroblasts. In mouse models of PPF, the mimics have reversed established fibrosis and restored lung architecture.
“The discovery that we could actually reverse the fibrosis was very exciting,” Dr. Hagood says. “This clinician-researcher collaboration is a potential game-changer for those facing the grim reality of PPF and other forms of chronic fibrosis.”
With funding from Harrington Discovery Institute, Drs. Hagood, Freeman, and their colleagues are now testing the effectiveness of their developmental peptide drug, mPep, in precision-cut lung slices generated from donor human lungs with the goal of developing a first-in-class therapeutic agent to reverse PPF.
Dr. Hagood adds that if successful, the mPep strategy may also be relevant in the future for additional indications including fibrosis of the liver, kidneys, and heart.