A researcher at The Center for Advanced Lung Care at Brown University Health has led the publication of groundbreaking new findings in the prestigious journal Science Translational Medicine that could lead to new treatments for pulmonary fibrosis, a serious and often progressive lung disease with limited treatment options.
The study, a multi-institutional collaboration between investigators at Brigham and Women's Hospital, Massachusetts General Hospital, the University of Utah, and Vettore Biosciences, was led by William Oldham, MD, PhD, ATSF, a pulmonologist in the Division of Pulmonary, Critical Care and Sleep Medicine at Brown University Health and physician-scientist at the Center for Advanced Lung Care.
Pulmonary fibrosis causes scarring in the lungs, making it increasingly difficult for patients to breathe over time. Current therapies can slow progression of the disease but do not reverse the damage, underscoring the urgent need for new treatment approaches.
The Brown University Health-led study focused on how lung scar tissue is made, specifically by specialized cells called myofibroblasts. The research showed that two proteins involved in cellular metabolism — known as monocarboxylate transporters, or MCT1 and MCT4 — appear to be critical in driving the scarring process. When these transporters were blocked in both human lung cells and mouse models, a significant reduction in fibrosis-related activity and lung damage resulted.
“These results identify a promising new pathway that could potentially be targeted to treat pulmonary fibrosis,” said Dr. Oldham. “By interrupting how these cells process and transport energy-related molecules, we are able to reduce the activity that leads to lung scarring in experimental models.”
The study also identified a newer investigational compound known as VB253, which targets MCT4. In preclinical models, the compound showed effectiveness comparable to currently approved antifibrotic therapies.
Research showed that blocking MCT activity improved how cells generate energy, reduced harmful oxidative stress, and decreased the buildup of fibrotic tissue in the lungs.
“These findings highlight the cutting-edge translational research underway within Brown University Health’s Division of Pulmonary, Critical Care and Sleep Medicine where clinicians and scientists work together to accelerate discoveries that could improve patient care. This publication reflects the strength of our physician-scientist programs and our commitment to advancing therapies for complex lung diseases and bringing hope to patients who currently have very limited options,” said Corey Ventetuolo, MD, MS, ATSF, FAHA, to serve as Director of the Division of Pulmonary, Critical Care and Sleep Medicine at Brown University Health and the Warren Alpert Medical School of Brown University.
Pulmonary fibrosis affects tens of thousands of Americans each year and can significantly impact quality of life and long-term survival. Researchers say further studies will be needed before MCT-targeting therapies can be tested broadly in patients, but the findings represent an important step toward expanding future treatment possibilities.
The study also featured researchers from Thomas Jefferson University, the University of Maryland, and the University of Pittsburgh and their respective laboratories. It can be found here in Science Translational Medicine.