New approaches to asthma treatment

Southampton’s researchers have discovered how a gene for susceptibility to asthma contributes to the development of the disease. Their work sheds light on how the condition develops in young children and offers the potential for new treatments for asthma and other serious illnesses.

Around 5.4 million people in the UK are currently receiving treatment for asthma, a potentially life-threatening condition that can have a big impact on people’s daily lives.

The asthma susceptibility gene ADAM33 was discovered in 2002 by Professor Stephen Holgate, in collaboration with two US companies, The Genome Therapeutics Corporation and the pharmaceutical company Schering Plough. It is associated both with the early life origins of asthma and with impaired lung function. The Southampton study described the biological function of the gene for the first time, providing new insight into the progression and development of asthma. The ADAM33 protein is usually tethered in the cell membrane, but in asthma this tether is broken.

Since ADAM33 is an enzyme, the research theme reasoned that the untethered enzyme could attack proteins it should not normally encounter. They discovered that the cells lining the inner surface of blood vessels become a target for ADAM33, causing formation of new blood vessels in a process called ‘angiogenesis’. These blood vessels can carry more inflammatory cells into the airways, causing swelling and changes in airway structure, which in turn, results in breathing difficulties.

Professor Donna Davies, one of the project’s leads comments ‘Treatments which specifically target the ADAM33 enzyme may be effective in modifying the natural history of the disease. However, the importance of angiogenesis in many physiological and pathological processes broadens the range of the diseases in which the enzyme could be implicated, the most obvious being cancer and atherosclerosis, or thickening of the arteries’