Ezetimibe Therapy Shows Effective Outcome in Idiopathic Pulmonary Fibrosis: Study

The results of the study found ezetimibe to inhibit myofibroblast differentiation by modulating the mechanistic target of rapamycin complex 1 (mTORC1) and restoring autophagy which is crucial for cellular homeostasis and repair. Also, serum response factor, identified as a key autophagic substrate was observed to be a significant downstream effector in this pathway. In the mouse model, ezetimibe significantly reduced bleomycin-induced pulmonary fibrosis which demonstrated a clear therapeutic benefit. The improved autophagic flux observed in the lung samples of these mice further supported these findings.

The clinical data from the idiopathic pulmonary fibrosis patients corroborated these experimental results. Regular use of ezetimibe was associated with a marked decrease in all-cause mortality and a slower reduction in lung function that highlights the potential of the drug as a pivotal treatment option for IPF.

This study introduces ezetimibe as a new candidate for the treatment of idiopathic pulmonary fibrosis with limited therapeutic options and a poor prognosis. Ezetimibe may offer a dual benefit of cholesterol management and pulmonary fibrosis reduction by targeting the mTORC1–autophagy axis and controlling intracellular cholesterol distribution. The findings pave the way for further clinical trials to establish the efficacy and safety of ezetimibe in IPF patients which can improve outcomes for the individuals affected by this chronic and often fatal lung condition.

Reference:

Lee, C., Kwak, S. H., Han, J., Shin, J. H., Yoo, B., Lee, Y. S., Park, J. S., Lim, B. J., Lee, J. G., Kim, Y. S., Kim, S. Y., & Bae, S. H. (2024). Repositioning of ezetimibe for the treatment of idiopathic pulmonary fibrosis. In European Respiratory Journal (Vol. 63, Issue 5, p. 2300580). European Respiratory Society (ERS). https://doi.org/10.1183/13993003.00580-2023