New research into the workings of a rogue protein made by a gene associated with asthma may lead to a medicine that could prevent the development of the disease in children and stop it from getting worse in adulthood.
Scientists have discovered that protein produced by the ADAM33 gene exacerbates inflammation and airway remodeling, which causes breathing difficulties due to additional muscles and blood vessels forming around the airways of asthma patients.
Previously, it was generally believed that allergens caused the airways to narrow, resulting in inflammation and asthma attacks, although scientists could not explain why only some people with allergies get asthma.
“We think this is a major step forward,” said Dr. Hans Michael Haitchi, who led the early-stage research at Britain’s University of Southampton.
“We’ve shown that this rogue protein ADAM33 actually causes airway remodeling before inflammation and then with allergens it causes even more remodeling and inflammation,” he told Allergic Living.
Next steps for the scientists, who have so far conducted their experiments only on mice, include developing molecules that can block ADAM33 and starting pre-clinical studies of new inhibitors.
“If we could prevent this remodeling by blocking ADAM 33 relatively early in life and test people who have this rogue protein in their lungs, or maybe just in their sputum, we could develop a specific treatment,” Dr. Haitchi said.
Respiratory difficulties associated with asthma are usually treated with a controller inhaler containing a low dose of corticosteroids to manage symptoms and a reliever inhaler to stop acute attacks.
The ADAM33 gene makes a protein, which normally sticks to the membrane of the muscle cells that surround the airways, Dr. Haitchi said.
“In asthma, we’ve shown that if this protein loses the anchor in the membrane, it becomes a rogue protein that actually floats around the lung, and then it can cause damage and this change in the airways.”
When researchers switched off the gene or the protein, they saw a complete reversal of the remodeling process. In mice that had no ADAM33 gene, but were exposed to allergens, they showed less airway remodeling, 60 percent less twitchiness of the airways and 30 percent less inflammation, Dr. Haitchi explained.
“If we could prevent this remodeling by blocking ADAM 33 relatively early in life and test people who have this rogue protein in their lungs, or maybe just in their sputum, we could develop a specific treatment,” he said.