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White blood cell plays key role in body's excessive repair response to asthma - Airway scarring can be disrupted by targeting eosinophils
September 30, 2003Researchers in London and Montreal report today that they have discovered an important link in the development of the body's response to allergic asthma.
They have found that one type of white blood cell, an eosinophil, which was known to cause inflammation of lung airways, is also responsible for driving the process which leads to an excessive 'repair response' by the body.
The response, which is called airway remodelling, causes structural changes in the airway walls and can sometimes lead to permanent scarring and narrowing of the airways, resulting in worse and repeated asthma episodes for sufferers.
The team of scientists from Imperial College London, the Royal Brompton Hospital, London, Guys Hospital, London, McGill University Hospital Centre, Montreal, and St Barts and the Royal London Hospitals Trust, report that the damaging effects of eosinophils in the remodelling process can be significantly reduced by injection of a single specific antibody.
Their research published today in the Journal of Clinical Investigation shows that the monoclonal antibody anti-Interleukin-5 (mepolizumab) both reduces the number of eosinophils in the bronchi and significantly decreases the deposition of special proteins associated with the remodelling process.
The scientists hope their work may lead to the development of 'really effective' new asthma treatments that work by interfering with the remodelling process.
Leader of the research, Professor Barry Kay, of Imperial College London and the Royal Brompton Hospital, comments: "This research could be of considerable long term benefit in developing more effective treatments in asthma. We already know that eosinophils cause inflammation in the bronchi, but it is the subsequent repair process which may be more important in long term chronic disease.
"In the future, drugs may be available which completely interfere with the process of scarring or re-modelling, and may prove beneficial in the long term treatment of asthma."
Professor Kay adds: "Anti-IL-5 will not be a magic bullet for asthma sufferers, but it could be an important first step in developing really effective drugs which interfere with re-modelling."
Anti-IL5, which removes Interleukin-5, a key molecule in eosinophil development, was given to mild asthmatics as part of a randomised, double blind, placebo controlled protocol.
The 24 patients in the study received three infusions of either the antibody or a placebo dummy injection one month apart, and had a biopsy of the lining of the breathing tubes before and after each infusion. The scientists measured levels of extra cellular matrix (ECM) proteins in the biopsy samples, which indicated the levels of remodelling activity in the airway.
The research was supported by grants from GlaxoSmithKline plc and the Wellcome Trust.
Imperial College, University of London
The team of scientists from Imperial College London, the Royal Brompton Hospital, London, Guys Hospital, London, McGill University Hospital Centre, Montreal, and St Barts and the Royal London Hospitals Trust, report that the damaging effects of eosinophils in the remodelling process can be significantly reduced by injection of a single specific antibody.
Their research published today in the Journal of Clinical Investigation shows that the monoclonal antibody anti-Interleukin-5 (mepolizumab) both reduces the number of eosinophils in the bronchi and significantly decreases the deposition of special proteins associated with the remodelling process.
The scientists hope their work may lead to the development of 'really effective' new asthma treatments that work by interfering with the remodelling process.
Leader of the research, Professor Barry Kay, of Imperial College London and the Royal Brompton Hospital, comments: "This research could be of considerable long term benefit in developing more effective treatments in asthma. We already know that eosinophils cause inflammation in the bronchi, but it is the subsequent repair process which may be more important in long term chronic disease.
"In the future, drugs may be available which completely interfere with the process of scarring or re-modelling, and may prove beneficial in the long term treatment of asthma."
Professor Kay adds: "Anti-IL-5 will not be a magic bullet for asthma sufferers, but it could be an important first step in developing really effective drugs which interfere with re-modelling."
Anti-IL5, which removes Interleukin-5, a key molecule in eosinophil development, was given to mild asthmatics as part of a randomised, double blind, placebo controlled protocol.
The 24 patients in the study received three infusions of either the antibody or a placebo dummy injection one month apart, and had a biopsy of the lining of the breathing tubes before and after each infusion. The scientists measured levels of extra cellular matrix (ECM) proteins in the biopsy samples, which indicated the levels of remodelling activity in the airway.
The research was supported by grants from GlaxoSmithKline plc and the Wellcome Trust.
Imperial College, University of London
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Aileron collaborates study in Nature: Stapled peptides inhibit Notch1 transcription factor
This research validates the potential for Stapled Peptides to modulate key intracellular biological targets, such as transcription factors, that have not been addressable with current small molecule or biologic drug modalities.
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