Discovery shows potential for new severe asthma treatment

Jun 15 2009

Scientists from King's College London and Imperial College London believe they have discovered a key element in the development of chronic asthma. Their research has been published in a new paper in the journal Proceedings of the National Academy of Sciences to explain why the structure and function of asthmatic airways are changed or ''remodelled'' and how this contributes to chronic asthma.

Remodelling occurs when the small airways in the lungs of people change gradually with time as their lungs respond to the presence of particles such as dust, pollen and mould in the air they breathe. These changes can also be compounded by viruses and bacteria.

Airway remodelling is apparent even in the lungs of young children with asthma, and can make the condition almost impossible to control. An important aspect of airway remodelling is changes to the muscle cells which line our airways. In people with asthma, these cells 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.

Dr Elaine Vickers, Research Relations Manager at Asthma UK says: 'This research into the causes of asthma provides us with vital clues as to how such symptoms could be stopped and it has uncovered important information, which we hope will lead to the creation of effective new treatments for the millions of people in the UK affected by asthma symptoms.'

Professor Tak Lee, Head of the Division of Asthma and Allergy Research at King's, who led the research, comments: 'It is widely believed that this remodelling in Asthma is in large part responsible for the chronicity of the disease. There are many features responsible for remodelling but a key component of this process involves an increased amount of smooth muscle in the airways.'

This research was also supported by the Medical Research Council; the Dr Hadwen Trust for Humane Research; the Guy's and St Thomas' NHS Foundation Trust, King's College London National Institute for Health Research Biomedical Research Centre, and Asthma UK.

These experiments have shown that cells derived from asthmatic patients are very abnormal. The recent work by researchers from the MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London and Imperial College London has found for the first time a unifying mechanism that may account for many features of this aspect of the remodelling process.

Professor Tak Lee and colleagues have 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. They believe that they have discovered a key reason why muscle cells in the lungs of people with asthma become over-sensitive.

The amount of calcium in muscle cells is controlled by a series of channels and pumps that either increase or decreased 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 Asthma UK and Dr Hadwen Trust for Humane Research-supported scientists studied muscle 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. The scientists compared these cells to those from people who either had asthma or didn't have asthma at all. 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 play 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 which can make some people's asthma almost impossible to control.

Dr Sebastien Farnaud, Science Director at the Dr Hadwen Trust for Humane Research says: 'This is a really exciting development in asthma research because it brings us a step further to replacing potentially misleading animal models with more human-relevant approaches that could hasten the development of more appropriate and effective treatments.'