A Virginia Tech team has identified a promising new therapeutic strategy for idiopathic pulmonary fibrosis (IPF), showing that blocking two proteins can halt and even reverse lung scarring in pre-clinical models.
A new study in the journal Theranostics , led by senior author Yassine Sassi, an assistant professor with the Fralin Biomedical Research Institute , found that simultaneously inhibiting two proteins — ID1 and ID3 — significantly reduced lung scarring and improved lung function across multiple experimental systems.
IPF is a progressive disease in which scar tissue builds up in the lungs, making it increasingly difficult to breathe. The disease affects an estimated 100,000 people in the United States, with about 30,000 to 40,000 new cases diagnosed each year, according to the National Institutes of Health. Existing therapies can slow disease progression but do not stop or reverse it, and most patients survive only three to five years after diagnosis.
"This work identifies ID1 and ID3 as important drivers of fibrosis and provides a strong foundation for developing new therapeutic approaches, including drug development and targeted delivery strategies," said Sassi.
The research, driven by first author Samar Antar, a postdoctoral fellow in the Sassi lab, combined analyses of human lung tissue and cells from patients with IPF with several experimental models in mice. The team found that ID1 and ID3 levels are elevated in diseased lung fibroblasts — cells that drive the formation of scar tissue.
When both proteins were inhibited, fibroblast activation was significantly reduced, limiting the processes that lead to pulmonary fibrosis.
The researchers tested multiple strategies to block ID1 and ID3, including a small-molecule drug and a targeted gene therapy approach. Across these approaches, inhibition of the proteins not only slowed disease progression but also reduced established pulmonary fibrosis in mice and improved lung function.
In some experiments, the therapeutic effects were comparable to or exceeded those of currently approved antifibrotic drugs.
The study also sheds light on how these proteins contribute to disease. ID1 and ID3 regulate fibroblast growth through cell cycle pathways and promote scarring through MEK/ERK signaling — key mechanisms underlying pulmonary fibrosis.
"By targeting these pathways, we can directly interrupt the cellular processes that drive fibrosis," said Sassi, who is also an assistant professor in the Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine.
The study included collaborators from the Icahn School of Medicine at Mount Sinai, Boston University, Memorial Sloan Kettering Cancer Center, and Rutgers New Jersey Medical School.
The findings point to ID1 and ID3 as targets for new treatments and highlight multiple potential paths forward, including drug development and targeted delivery strategies.
