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  • Ezetimibe Therapy...

Ezetimibe Therapy Shows Effective Outcome in Idiopathic Pulmonary Fibrosis: Study

Written By : Jacinthlyn Sylvia |Medically Reviewed By : Dr. Kamal Kant Kohli Published On 2024-06-20T21:15:10+05:30  |  Updated On 21 Jun 2024 12:15 PM IST
Weaning of non COPD patients at high-risk of extubation failure assessed by lung ultrasound
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A recent study published in the European Respiratory Journal identified the cholesterol-lowering drug ezetimibe which was already approved by the European Medicines Agency, as a potent activator of autophagy with potential therapeutic benefits for idiopathic pulmonary fibrosis (IPF). The previously known role of ezetimibe as an inhibitor of Niemann–Pick C1-like intracellular cholesterol transporter 1 has now been expanded to include its capacity to combat this debilitating lung disease.

The research team conducted extensive in vitro and in vivo experiments to explore the efficacy of ezetimibe against pulmonary fibrosis. Primary lung fibroblasts from both human and mouse sources were utilized for mechanistic studies. Through mRNA sequencing and gene set enrichment analysis of these fibroblasts, the research uncovered the underlying therapeutic mechanisms of ezetimibe. Also, a bleomycin-induced pulmonary fibrosis mouse model was employed to assess the efficacy of this drug in a living organism. Autophagic flux was measured using transgenic mice expressing tandem fluorescent-tagged microtubule-associated protein 1 light chain 3. The medical records of IPF patients from three different hospitals were retrospectively reviewed to evaluate the real-world impact of ezetimibe on survival and lung function.

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

European Respiratory JournalEzetimibeidiopathic pulmonary fibrosis
Source : European Respiratory Journal
Jacinthlyn Sylvia
Jacinthlyn Sylvia

    Neuroscience Masters graduate

    Jacinthlyn Sylvia, a Neuroscience Master's graduate from Chennai has worked extensively in deciphering the neurobiology of cognition and motor control in aging. She also has spread-out exposure to Neurosurgery from her Bachelor’s. She is currently involved in active Neuro-Oncology research. She is an upcoming neuroscientist with a fiery passion for writing. Her news cover at Medical Dialogues feature recent discoveries and updates from the healthcare and biomedical research fields. She can be reached at editorial@medicaldialogues.in

    Dr. Kamal Kant Kohli
    Dr. Kamal Kant Kohli

    Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751

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