Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects.
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http://dx.doi.org/10.18632/oncotarget.17114 | DOI Listing |
Toxicol Appl Pharmacol
December 2024
College of Medicine, Graduate School, Kyung Hee University, 02447, Republic of Korea; Division of Cardiology, Department of Internal Medicine, Kyung-Hee University Hospital, Kyung Hee University, 02447, Republic of Korea. Electronic address:
In the current study, we dosed Didecyldimethylammonium chloride (DDAC) in mice by pharyngeal aspiration for 28 days or 90 days (weekly) and tried to elucidate the relationship between lamellar body formation and the lesions. When exposed for 28 days (0, 5, 10, 50, and 100 μg/head), all the mice in the 50 and 100 μg/head groups died since Day 2 after the third dosing (Day 16 after the first dosing). Edema, necrosis of bronchiolar and alveolar epithelium, and fibrinous exudate were observed in the lungs of all the dead mice, and chronic inflammatory lesions were observed in the lung tissues of alive mice.
View Article and Find Full Text PDFClin Radiol
November 2024
School of Medicine, Cork University Hospital, Cork, Ireland; Department of Respiratory Medicine, Cork University Hospital, Cork, Ireland.
Aim: Idiopathic pulmonary fibrosis (IPF) is a debilitating and fatal lung disease. Changes in body composition potentially correlate with outcomes in patients with IPF.
Materials And Methods: Patients with IPF on antifibrotic treatment attending a single institution were identified and retrospectively evaluated (n=84).
Life Sci
December 2024
"Aurel Ardelean" Institute of Life Sciences, "Vasile Goldis" Western University of Arad, 310144 Arad, Romania; Department of Histology, Faculty of Medicine, "Vasile Goldis" Western University of Arad, 310144 Arad, Romania. Electronic address:
Aims: COVID-19, caused by the SARS-CoV-2 virus, can lead to serious lung conditions, notably interstitial pulmonary fibrosis.
Main Methods: Our study tracked the progression of fibrosis markers in serial bronchoalveolar lavage (BAL) measurements collected from 16 COVID-19 patients at 1, 3, and 6 months post-infection. Additionally, BAL samples from 10 healthy control subjects were included.
J Evid Based Med
December 2024
Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Purpose: To develop and validate the patient-reported outcome scale for idiopathic pulmonary fibrosis (IPF-PRO) to provide a reliable and scientific measure for clinical trials on idiopathic pulmonary fibrosis (IPF).
Methods: We analyzed the relevant literature and medical records and conducted interviews and panel discussions to develop the conceptual framework and generate the item pool. We subjected the collected items to removal, mergence, or modification to form the initial scale through a qualitative review by experts and patients.
Am J Case Rep
December 2024
Department of Internal Medicine, Groene Hart Hospital, Gouda, Netherlands.
BACKGROUND IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease potentially affecting every part of the human body. Because of variability in clinical presentation, IgG4-RD can be challenging to diagnose. Untreated disease can lead to irreversible organ damage such as fibrosis.
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