STING Agonist Induced Innate Immune Responses Drive Anti-Respiratory Virus Activity with Limited Antiviral Efficacy .

The emergence of SARS-CoV-2 and seasonal outbreaks of other respiratory viruses highlight the urgent need for broad-spectrum antivirals to treat respiratory tract infections. Stimulator of interferon genes (STING) is a key component of innate immune signaling and plays a critical role in protection of the host against viral infections. Previously the STING agonist diABZI-4, a diamidobenzimidazole-based compound, demonstrated protection against SARS-CoV-2 both and .

A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled αvβ6 integrin inhibitor.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with poor prognosis and a significant unmet medical need. This study evaluated the safety, pharmacokinetics (PK) and target engagement in the lungs, of GSK3008348, a novel inhaled alpha-v beta-6 (αvβ6) integrin inhibitor, in participants with IPF.

Methods: This was a phase 1b, randomised, double-blind (sponsor unblind) study, conducted in the UK (two clinical sites, one imaging unit) between June 2017 and July 2018 (NCT03069989).

Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort.

Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was assessed in 145 newly-diagnosed individuals with IPF.

Patient-reported distress can aid clinical decision-making in idiopathic pulmonary fibrosis: analysis of the PROFILE cohort.

Idiopathic pulmonary fibrosis is a progressive and fatal interstitial lung disease. We aimed to determine if patient response to a palliative assessment survey could predict disease progression or death.We undertook a cross-sectional study in a UK clinical cohort of incident cases.

A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis.

Phosphatidylinositol 3-kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is a potent inhibitor of PI3K/mTOR.A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study of omipalisib in subjects with IPF was conducted (NCT01725139) to test safety, tolerability, pharmacokinetics and pharmacodynamics.

Safety, tolerability and pharmacokinetics of GSK3008348, a novel integrin αvβ6 inhibitor, in healthy participants.

Purpose: Inhaled drug delivery is an attractive route by which to deliver drugs to lungs of patients with idiopathic pulmonary fibrosis (IPF). GSK3008348 is a potent and selective small molecule being developed as the first inhaled inhibitor of the αvβ6 integrin for the treatment of IPF. The phase 1 first-time-in-human clinical trial (NCT02612051) presented here was designed to investigate the safety, tolerability and pharmacokinetic (PK) profile of single doses of GSK3008348 in healthy participants.

The topical study of inhaled drug (salbutamol) delivery in idiopathic pulmonary fibrosis.

Background: Our aim was to investigate total and regional lung delivery of salbutamol in subjects with idiopathic pulmonary fibrosis (IPF).

Methods: The TOPICAL study was a 4-period, partially-randomised, controlled, crossover study to investigate four aerosolised approaches in IPF subjects. Nine subjects were randomised to receive Technetium-labelled monodisperse salbutamol (1.

Diverse functions of clusterin promote and protect against the development of pulmonary fibrosis.

Pulmonary fibrosis is a progressive scarring disorder of the lung with dismal prognosis and no curative therapy. Clusterin, an extracellular chaperone and regulator of cell functions, is reduced in bronchoalveolar lavage fluid of patients with pulmonary fibrosis. However, its distribution and role in normal and fibrotic human lung are incompletely characterized.

An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess potential biomarkers to predict outcomes for people with IPF.

Methods: PROFILE is a large prospective longitudinal cohort of treatment-naive patients with IPF.

Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study.

Background: Idiopathic pulmonary fibrosis, a progressive and inevitably fatal disorder, has a highly variable clinical course. Biomarkers that reflect disease activity are urgently needed to inform patient management and for use as biomarkers of therapeutic response (theragnostic biomarkers) in clinical trials. We aimed to determine whether dynamic change in markers of extracellular matrix (ECM) turnover predicts progression of idiopathic pulmonary fibrosis as determined by change in forced vital capacity and death.

Strategies for biomarker discovery in fibrotic disease.

The discovery and development of biomarkers for fibrotic diseases have potential utility in clinical decision-making as well as in pharmaceutical research and development. This review describes strategies for identifying diagnostic, prognostic and theranostic biomarkers. A range of technologies and platforms for biomarker discovery are highlighted, including several with specific relevance for fibrosis.