Janssen-Heininger, Anathy & Team's Study Demonstrates Potential Lung Fibrosis Therapy

July 11, 2018 by Jennifer Nachbur

New translational research led by UVM Professor Yvonne Janssen-Heininger, Ph.D., demonstrates a novel biological therapeutic candidate for regressing pulmonary fibrosis in a difficult-to-treat preclinical model of the disease, providing much-needed hope for the roughly 150,000 Americans suffering from this devastating condition.

Yvonne Janssen-Heininger, Ph.D., UVM Professor of Pathology & Laboratory Science. (Photo: Medical Communications)

New translational research, published in Nature Medicine, demonstrates a novel biological therapeutic candidate for regressing pulmonary fibrosis in a difficult-to-treat preclinical model of the disease, providing much-needed hope for the roughly 150,000 Americans suffering from this devastating condition.

A chronic, progressive disease marked by lung scarring that impedes breathing and the flow of oxygen to the bloodstream, idiopathic pulmonary fibrosis (IPF) results in approximately 40,000 deaths each year in the U.S. alone. Believed to be associated with aging, the disease is diagnosed annually in approximately 40,000 individuals between 40 and 70 years of age. Survival is typically only three to five years after diagnosis.

This study included an examination of IPF patient lung tissue, transgenic mouse models and direct administration of a therapy based off an enzyme called glutaredoxin-1 – or GLRX – to the airways of murine models of IPF. GLRX repairs damaged proteins and is inactivated in the lungs of IPF patients and results in poor lung function. Senior study author Yvonne Janssen-Heininger, Ph.D., and first author Vikas Anathy, Ph.D., of the University of Vermont’s Larner College of Medicine, and colleagues are inventors on a patent for GLRX, granted to the University of Vermont.

Though the exact mechanisms responsible for IPF have yet to be determined, oxidative stress is believed to play a critical role in modifying and altering the function of proteins or enzymes in various diseases, including IPF. However, the therapeutic potential for reversing the oxidative stress mediated modification of proteins was unknown. Janssen-Heininger and colleagues have discovered that GLRX is capable of reversing the oxidation of proteins, preventing the death of lung cells and ultimately, regressing pulmonary fibrosis in experimental models. The researchers believe that these positive effects raise the potential of GLRX as a therapeutic agent for IPF, which currently has limited treatment options.   

“This provides a strong rationale to develop inhaled glutaredoxin as a possible therapy for patients with lung fibrosis,” says Janssen-Heininger. She and the study authors state that further investigation will be needed to gain a deeper understanding of the activity associated with GLRX.

In addition to Janssen-Heininger and Anathy, coauthors on the study include: Karolyn Lahue; David Chapman; Shi Chia; Dylan Casey; Reem Aboushousha; Jos van der Velden; Evan Elko; Sidra Hoffman; David McMillan; Jane Jones; James Nolin; Sarah Abdalla; Robert Schneider; David Seward; Elle Roberson; Matthew Liptak; Morgan Cousins; Kelly Butnor; Douglas Taatjes; Ralph Budd; Charles Irvin; Ye-Shih Ho; Razq Hakem; Kevin Brown; Reiko Matsui; Markus Bachschmid; Jose L. Gomez; Naftali Kaminski; and Albert van der Vliet.

This therapy is being developed in collaboration with Celdara Medical, LLC, of Lebanon, N.H. and with support from the National Heart, Lung and Blood Institute of the National Institutes of Health under award numbers R44 HL129593-01 and R35HL135828.

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