The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis

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

Asbestos-related lung disease: An update

In this work, we describe both benign and malignant asbestos-related diseases and provide an updated review of recent advances in the field. It has long been appreciated that the inhalation of asbestos fibers causes several well-described respiratory diseases including pleural plaques, diffuse pleural thickening, asbestosis, lung cancer, and malignant pleural mesothelioma (MPM). However, despite this knowledge and stricter industrial controls, the incidence of these diseases continues to increase in many parts of the world. In fact, despite the introduction of strict limits early in the 20th century, the mortality rate due to MPM is still increasing in industrialized countries such as the United Kingdom and Australia. In this update we provide an overview of each disease entity while concentrating on the role that newer imaging techniques, including high-resolution computed tomography, magnetic resonance imaging, and positron emission tomography /computed tomography, play in the diagnosis of asbestos-related pleural and parenchymal diseases. As the incidence of MPM continues to increase in many parts of the world, this review also focuses on new approaches to the diagnosis and treatment of this devastating condition. A description of the potential use and limitations of biomarkers in the diagnosis and monitoring of the disease is included along with recent trial data examining novel vaccine-based biological therapies. © 2011 by Lippincott Williams & Wilkins