New research from the University of Southampton in England is set to expand scientists’ knowledge about why some people are more prone to develop asthma by analyzing a gene called ADAM33 – typically linked to the development of the disease and its characteristic airway “twitchiness.”
The gene is also believed to impact the airway architecture in young children’s lungs, perhaps from as early as before birth.
“We know that ADAM33 makes an enzyme, which is attached to cells in the airway muscles. In asthma, it has been found that this enzyme goes rogue from these cells and higher levels of the enzyme are associated with poorer lung function,” lead researcher Hans Michel Haitchi, associate professor in respiratory medicine at the university, said in a news release.
“We think that when it detaches it causes problems by affecting cells that shouldn’t come into contact with it and this results in subtle changes in the airway wall – called airway remodeling – involving over-growth of cells that cause the airways to narrow, among other asthma-associated changes. We also think that this airway remodeling can occur before birth, which is something we will focus on in the study,” Haitchi said.
“We want to see how the remodeling affects reactions to irritants such as allergens later in life. We think that babies born with airway remodeling will be more sensitive to allergens, such as house dust mites, leading to the symptoms of asthma,” Haitchi said.
The study will assess mice that were born with and without the rogue ADAM33 enzyme, exposing the mice to causes of allergic inflammation, like dust allergens or the interleukin-13 protein.
This strategy will allow researchers to grasp how the rogue enzyme causes airway remodeling, and is involved in lung inflammation caused by allergens early in life. The research team will employ novel genetic methods to analyze the lungs of the animals, with the expectation that they will lead to the discovery of new asthma disease-associated genes and respective proteins.
“Understanding how the ADAM33 enzyme causes airway remodeling before birth and the responses to environmental triggers such as allergens are the first steps in developing a treatment to stop this from happening,” Haitchi said. “Airway remodeling reduces the ability of the lungs to function, and is not prevented by current anti-inflammatory steroid therapy. Therefore, stopping this would prevent a harmful effect of asthma for many of the 5.4 million people in the U.K. with the condition.”
Samples from youngsters whose mothers have asthma, and children who have the condition themselves, will also be included in the study to determine how the ADAM33 enzyme interacts with the airway structure.
Samples will largely be collected from the National Institute for Health Research (NIHR) Southampton Respiratory Biomedical Research Unit and the NIHR/Wellcome Trust Clinical Research Facility at University Hospital Southampton NHS Foundation Trust.
The project is funded by the Medical Research Foundation and Asthma UK.
“Asthma is a complex condition, which is why we fund research like this to understand more about it,” said Dr. Samantha Walker, director of research and policy at Asthma UK. “This research is so important because, although we may not be able to change our genes, by better understanding them we may be able to stop their effects.
“This project has the potential to make a real difference to people’s lives in the future by preventing them from developing asthma in the first place – and with three people still dying every day in the U.K. as a result of an asthma attack, this is crucial,” Walker said.
Dr. Angela Hind, director of the Medical Research Foundation, added, “The Medical Research Foundation joined with Asthma UK to fund new research which will make a difference to people living with asthma and to support the next generation of asthma research leaders for the U.K. Dr. Haitchi is such a future leader and we have every hope that his research will provide important insights into the development of asthma.”