A new approach to combating asthma-induced bronchial remodeling

Patients with bronchial asthma suffer from attacks of shortness of breath caused by constricted airways. “Anti-inflammatory medications are usually given to treat this, although it isn’t quite clear how inflammation and constriction correlate,” says Professor Daniela Wenzel, head of the Department of Systems Physiology in the Faculty of Medicine at Ruhr University Bochum. “These medications often stop working at a certain point.” Furthermore, asthma patients often experience a thickening of the bronchial tissue due to the accumulation of collagen. Goblet cells also form in increasing numbers, producing mucus and making breathing even more difficult. Currently, there is no medication to counteract these changes.

Targeting the protein directly

The agent derived from Ardisia crenata prevented the remodeling of the bronchia in the study. It binds to a specific protein – the Gq protein – and thus inhibits it directly. “Other medications often target receptors for the Gq protein, but there are many different types of receptors,” explains Jennifer Dietrich, lead author of the study. “So, we decided to take a different approach and target the protein directly.”

Using a mouse model of chronic bronchial asthma, the researchers tested the agent for five weeks, during which it was administered directly into the lungs as a liquid. “We were able to see that the remodeling decreased, less collagen accumulated, and fewer mucus-producing goblet cells were present in the epithelial layer of the bronchial tissue,” says Dietrich. Tests on human collagen-producing cells revealed that they grew slower in the presence of the agent, even when stimulated by asthma-associated growth factors. Other tests on human mucus-producing lung cells showed that the agent reduced mucus secretion and production. These results were reproduced in experiments with lung sections from persons who had died from asthma.

A promising candidate for future treatment

“We know from past studies that the agent also prevents the extreme constriction of the bronchi,” says Daniela Wenzel. “This makes it a very promising candidate for future asthma treatments.” Once the agent binds to the Gq protein, it remains active there for several days, far longer than other agents that have been tested.

Cooperation partners

The teams at Ruhr University Bochum, University of Bonn, and Bonn University Hospital were joined in the study by researchers from Rutgers University in the USA.