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13 May 2008

30 April 2008

New approach in asthma research could replace animal tests and save lives

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World Asthma Day May 1st – Asthma affects 5.2 million people in the UK alone, with just over 1,300 deaths from asthma each year, one person every seven hours1 . Despite many decades of research, much of it on animals, there is still no cure and more effective treatments are urgently needed. However, the Dr Hadwen Trust’s non-animal project using fibre-optic technology and human volunteers could massively improve the relevance of asthma research.

Researchers at King’s College, London, funded by the Dr Hadwen Trust, are using biopsy samples of airway smooth muscle cells donated by asthma patients and healthy volunteers. This has been made newly possible because of the application of fibre-optic endobronchoscopy which allows the collection of tiny samples of normal and asthmatic lung tissue from human volunteers.

Until recently, lung tissue from asthmatic patients was rarely available because the techniques to obtain the cells simply had not been established. As a result, animal experiments have played a large but questionable role in asthma research. Now though, fibre-optic bronchoendoscopy is being applied to asthma research, a minimally invasive and safe procedure that involves inserting a fine flexible fibre into the lung, allowing easy sampling of tiny amounts of tissue without cutting the body open. Fibre-optics is an established technology, but using it in this way to sample airway tissues from the lungs of asthmatic patients and healthy volunteers, is a new and exciting development which is improving the relevance of asthma research without animals.

Replacing animals in asthma research is vital not just for animal welfare reasons, but also because animal ‘models’ of asthma so poorly replicate the real human condition. Guinea pigs, mice, rats and rabbits are routinely used, none of whom naturally suffer from asthma. Instead they are subjected to distressing lung sensitization as well as repeated abdominal injections to induce inflamed airways and allergic shortness of breath.

Unlike human asthma, these artificially induced symptoms in animals are temporary and fail to fully replicate all aspects of human asthma. Furthermore many of the results found in animal ‘models’ cannot be duplicated in humans. For example, there are marked differences in the major intracellular signalling pathways that drive changes in airway smooth muscle; murine airways lack a developed bronchial circulation compared with human airways, and there are significant variations in potassium ion (K+) channel currents expressed by human airway smooth muscle cells and those from rabbit or rat. This makes developments in a human–based research approach all the more vital.

The Dr Hadwen Trust-funded researchers at King’s College London are applying the latest imaging and genetic techniques to the human lung samples to study the way asthmatics handle calcium which controls the contraction of airway muscle. They have already established that calcium stores are depleted in the cells of asthmatics indicating an abnormality in their calcium control mechanisms. The genetic control of these processes is now under investigation, with a view to identifying possible therapeutic targets for correcting airway smooth muscle function in asthmatics.

Says Nicky Gordon, Dr Hadwen Trust Science Officer:

“Applying fibre optic technology to asthma research is a really exciting development, because it is the key to moving away from potentially misleading animal experiments by replacing them with more human-relevant approaches. As well as potentially saving the lives of thousands of animals globally, it’s really good news for patients because more reliable asthma research should hasten the development of more appropriate and effective treatments.”

Professor Tak H Lee, King’s College London research team, is hopeful that the new model will produce real benefits for asthma research. He says:

“Asthma affects millions of people in the UK and is now a major health priority. Answers to key questions concerning the pathology of asthma rely on access to precious biopsy samples from patients. New and exciting information is coming to light following the development of a technique to obtain airway tissue using fibre-optic endobronchoscopy from volunteers with and without asthma. Establishing the systematic use of this human airway tissue as a research tool will help to replace animal studies in the laboratory.”

Notes

1 Statistics from Asthma UK.

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