New therapeutic target for asthma, other lung disorders identified
A researcher has discovered a molecule's previously unknown role as a major trigger for airway remodeling, which impairs lung function, making the molecule a promising therapeutic target for chronic asthma, chronic obstructive pulmonary disease (COPD) and several other lung conditions.
La Jolla Institute for Allergy and Immunology researcher Michael Croft showed that blocking LIGHT's interactions with its two receptors significantly inhibited the process of airway remodeling in mouse models of chronic asthma.
Airway remodelling refers to inflammation-fueled structural changes in the lungs, including fibrosis, which can occur over time and result in declining lung function that strongly contributes to conditions such as COPD, chronic asthma, and several other respiratory disorders.
The finding marks Croft's second major discovery with therapeutic potential for asthma.
His previous finding, of a novel molecular mechanism driving lung inflammation, is the basis for a potential asthma treatment now in Phase II human clinical trials.
Current therapies for asthma and COPD primarily include corticosteroids, bronchodilators, and leukotriene antagonists, but these are thought to have little impact, if any, on airway remodeling, said Croft.
Croft said emerging data on the role of the tumor necrosis factor (TNF) super family of molecules in fueling inflammatory diseases, including his own finding on OX40 Ligand and its receptor's action in triggering inflammation in asthma, prompted him to take a close look at fellow TNF molecule, LIGHT.
"We hypothesised that LIGHT might be involved in driving aspects of lung inflammation or have a role in lung dysfunction that was different than our previous findings on OX40L," he said.
"As we were undertaking our studies, a report found that increased sputum LIGHT levels in people with asthma correlated with decreased lung function, which was in line with our thinking," he added.
Using two mouse models of chronic asthma and a therapeutic blocking strategy, Croft said he and his team "demonstrated a direct role for LIGHT in promoting and controlling the extent of remodeling in the lung."
The study is detailed in the prestigious journal, Nature Medicine.