Fibrosing lung diseases, also known as interstitial lung diseases (ILDs), are rare and serious disorders marked by progressive scarring of the lungs. One of the most severe forms is idiopathic pulmonary fibrosis (IPF), which gradually destroys lung function and currently has no cure other than lung transplantation. Available antifibrotic drugs, including nintedanib, pirfenidone, and more recently, nerandomilast, can slow progression but cannot stop or reverse the disease.

Researchers at the Center for Interstitial and Rare Lung Diseases at Justus Liebig University Giessen have identified the RNA-binding protein FUS (“Fused in Sarcoma”) as a promising new therapeutic target in IPF. Their study found that FUS is abnormally increased in cells from IPF patients, particularly in the cytoplasm, where it is linked to disease-driving activity in both lung fibroblasts and alveolar type II epithelial cells (AEC2).

High FUS levels promoted profibrotic signaling in fibroblasts, including collagen production and TGF-β signaling, while reducing or silencing FUS markedly suppressed these responses, especially excessive fibroblast growth. The data also suggest that the antifibrotic effects of nintedanib and pirfenidone are partly mediated through FUS-related mechanisms.

To test the therapeutic potential of FUS inhibition, the researchers used the antisense oligonucleotide ION363, which is already in clinical testing for amyotrophic lateral sclerosis (ALS). Lowering FUS with ION363 reduced profibrotic signaling in patient-derived IPF fibroblasts and in living human IPF lung tissue cultured as high-precision cut lung slices.

Importantly, FUS inhibition also benefited alveolar epithelial cells. It restored the surfactant gene expression and improved the regenerative capacity of AEC2 in patient-derived alveolospheres / alveolar organoid models.

Together, these findings identify FUS as a promising therapeutic target in IPF. In preclinical human models, inhibiting FUS not only reduced fibrosis-related processes but also supported epithelial protection and repair, highlighting its potential for future treatment strategies.

Find the full article here: https://www.nature.com/articles/s41392-026-02585-9