Anti-cholesterol drug 'Ezetimib' reduces lung fibrosis progression risk by up to 62%
Jul 17, 2024
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A research team led by Professor Kim Song-yi and Instructor Lee Chan-ho of the Department of Respiratory Medicine at Severance Hospital, Professor Kwak Se-hyun of the Department of Respiratory and Allergy at Yongin Severance Hospital, and Professor Bae Soo-han of the Department of Medical Life Sciences at Yonsei University Medical School said that if patients with idiopathic pulmonary fibrosis take ezetimibe, the risk of death decreases by up to 62%.
Pulmonary fibrosis is a phenomenon in which the lungs harden, causing inflammation and recovery of the lungs like a scab sitting in the process of healing the wound. Pulmonary fibrosis is often called idiopathic pulmonary fibrosis because the cause is often clear, such as infection, autoimmune disease, and radiation therapy, but some are called idiopathic because the cause is unknown.
After diagnosis, anti-fibrotic drugs pirfenidone and nintedanib are used to slow progression to intractable diseases with an expected survival period of about 2 to 4 years. To date, transplantation is the only treatment method.
The research team confirmed the therapeutic effect of ezetimib, an anti-cholesterol drug, on idiopathic pulmonary fibrosis. Ezetimib is mainly used in patients with hyperlipidemia and myocardial infarction to lower LDL cholesterol, but it has also been found to activate autophagy. Autophagy is a collective term for the process by which cells break down certain substances or organelles in cells, and is a phenomenon in which cells decompose when organelles or proteins are excessive or damaged to supplement nutrients and energy. This study focused on the fact that patients with idiopathic pulmonary fibrosis have poor autophagy function.
First, lung fibroblasts were analyzed transcriptome to confirm the process by which ezetimib inhibits fibrosis. When ezetimib regulates cellular cholesterol, it activates autophagy by secreting the Mammalian Target of Rapamycin Complex1 (mTORC1) enzyme involved in cell physiological phenomena. Autophagy activation removed the SRF protein causing fibrosis. These processes were also confirmed in mouse models.
The research team continued to investigate whether Ezetimib was effective in real patients. We statistically analyzed the prognosis of 529 patients with idiopathic pulmonary fibrosis who took ezetimibe. Patients were divided into groups that took pirfenidone only, groups that took ezetimibe only, and groups that took pirfenidone and ezetimibe together to examine treatment outcomes.
The ezetimib group, pirfenidone, and ezetimib group had a lower risk of death by 62% and 45%, respectively, when compared to the pirfenidone group. In addition, when comparing lung capacity and gas diffusion capacity according to taking ezetimib among patients taking pirfenidone, taking ezetimib could suppress the decrease in lung function by up to 60%.
Lecturer Lee Chan-ho said, `It has been revealed that removing SRF protein by activating autophagy in pulmonary fibroblasts is a way to suppress pulmonary fibrosis,' and added, `We will work hard to confirm the effectiveness of EZTIMIV through follow-up studies such as big data analysis by the National Health Insurance Corporation.' The results of this study were recently published in the international journal 『The European Respiratory Journal』 (IF 24.9).
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