Breakthrough in understanding of severe asthma has potential for new treatment

Professor Tak Lee, Head of the Division of Asthma and Allergy Research at King's College London and his colleageus have been studying why the small airways in the lungs of asthmatics, even young children suffering from asthma, change shape with time as their lungs respond to the presence of particles such as dust, pollen and mould in the air they breathe. An important aspect of this airway ‘remodelling’ is changes to the muscle cells that line the airways which tend to multiply and become larger, increasing their ability to squeeze the airways and cause breathing difficulties. There is no known way of reversing airway remodelling once it has occurred and it is widely believed that it is in large part responsible for the chronicity of the disease.

The researchers focused their attention on the movement of calcium in and out of muscle cells, because calcium is the most plentiful mineral in the human body and it regulates many cellular activities. The amount of calcium in muscle cells is controlled by a series of channels and pumps that either increase or decrease calcium levels. One of these pumps is called SERCA2. It relaxes muscle cells by pumping calcium out of the main body of the cell, the cytoplasm, and into an internal compartment called the sarcoplasmic reticulum.
The reserachers compared the cells from the airways of people with moderate asthma, who experience daily asthma symptoms and need both preventer and reliever inhalers to keep their symptoms under control to those from people who didn't have asthma. They discovered that in people with moderate asthma SERCA2 levels were reduced, lowering the cells' capacity to remove calcium from the cytoplasm. They also found that if they removed SERCA2 from the cells of people who didn't have asthma, these cells started to behave more like asthma cells.

These discoveries suggest that a lack of SERCA2 in airway muscle cells plays an important role in causing asthma symptoms. Professor Lee suggests that replacing SERCA2 in these cells might be an effective way of creating new asthma treatments to reduce asthma symptoms and prevent the long-term lung changes that can make some people's asthma almost impossible to control.

This research was published in the Journal Proceedings of the National Academy of Sciences.

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First Published in September 2009

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