Asthma breakthrough uncovers key mechanism behind airway thickening
New research from the La Jolla Institute for Immunology has brought a novel, long-term treatment for severe asthma a step closer. Building on a decade of work, the new findings present a potential way to block the thickening of airway muscle tissue seen in chronic asthma patients.
A foundational study published in 2011 revealed a particular immune molecule plays a crucial role in the thickening of asthma patients' airways. Dubbed LIGHT, the protein is produced by immune T cells in excessive volumes when the body is presented with an allergen.
In patients suffering from chronic asthma, researchers have detected a progressive thickening of the smooth muscle in their airways. Referred to as "tissue remodeling," this process essentially adds to a patient's breathing problems over time, making their asthma get worse and worse.
"Current treatments for asthma are mainly to suppress symptoms and subdue allergic inflammation," explained Haruka Miki, a researcher working on study. "No treatment has been developed to fundamentally cure asthma. Even when inflammation is suppressed by current treatments, underlying airway hyperresponsiveness and airway tissue changes (airway remodeling) often remain, especially in severe asthma."
For several years the La Jolla team knew the LIGHT protein was fundamentally involved in these airway tissue changes. But the exact mechanisms at play were still unclear.
In this new study, published in the Journal of Allergy and Clinical Immunology, the researchers looked at two key receptors expressed on smooth muscle cells in the airway. These two receptors are how LIGHT molecules bind to the airway muscle cells.
The big discovery here was that one of the receptors (LTβR) is vital for tissue remodeling to take place. Senior author on the study, Matthew Croft, said mouse studies revealed LIGHT molecules binding with LTβR receptors trigger the airway thickening seen in chronic asthma.
"When those cells in the lungs cannot express LTβR, then essentially all of the hallmarks of the smooth muscle response associated with severe asthma are either gone or they're highly limited," added Croft.
While this discovery doesn't immediately mean we should expect a new treatment for severe asthma over the next year or two, it does lay the foundations for entirely novel therapeutics designed to fix the structural airway problems that are associated with the chronic condition.
If a treatment can be found to block LIGHT from binding to LTβR, or reduce LTβR volumes of airway cells, then one of the main physiological characteristics of chronic asthma could be prevented. And the La Jolla team is already working with a pharmaceutical company to translate these findings into a future drug treatment.
"This is a very, very significant finding," said Croft. "This research gives us a better understanding of the potential of therapeutic targeting of LIGHT and what we might do to relieve some of the symptoms and some of the inflammatory features seen in patients who have severe asthma."
The new study was published in the Journal of Allergy and Clinical Immunology.