The Gene Dilemma: How a cold got in the way

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The Independent Online
THE RESULTS of Britain's first gene therapy trial for cystic fibrosis, Britain's most common inherited disease, have been delayed - by the common cold.

Dr Duncan Geddes, director of respiratory medicine at the National Heart and Lung Hospital in London, started treating 12 patients in September. Yesterday he said: 'All it needs is for someone to get a cold and that puts the measurements off for a month - and there are lots of colds going around.'

Outwardly, the cystic fibrosis gene transplant appears a simple procedure, which involves each volunteer sniffing briefly from a nasal spray. The sophistication lies in the genetic engineering that has produced the material sprayed, consisting of fatty globules containing billions of copies of the intact cystic fibrosis gene. The hope is that the globules - known as liposomes - will merge with the fatty outer membrane of the cells lining the inner surface of the nose, carrying their precious genetic cargo into the cells.

Dr Geddes said: 'They get the inhalation once, and then we test repeatedly over the following month. We are testing the electric charge on the surface of the lining of the nose; and using a sort of 'pipe cleaner' to brush away nose cells to look at the gene, and whether it has been translated into protein.'

In what is known as a double blind trial, some patients are receiving sprays which do not contain genes as a 'control' to check that if there is improvement the effect is truly because of the gene transplant. To prevent unconscious bias, Dr Geddes does not know which patients have received the genes and which the placebo and he will be told only after measurements are complete.

If the procedure works, Dr Geddes is cautious about describing it as a 'cure' for doses will have to be given repeatedly. Cystic fibrosis affects more than 7,000 children and young adults, whose lungs clog with thick mucus which provides a perfect breeding ground for bacteria and leaves them open to recurrent infections. These scar the lungs, leaving patients breathless, and eventually lead to lung failure. CF also blocks the secretion of digestive enzymes.

There is currently no cure and sufferers used to die in early childhood. With modern antibiotics and intensive nursing, they now have much longer life expectancy. But their lives are dominated by a constant regime of having to take up to 70 tablets a day, to stop chest infections, improve breathing, and to assist in digestion. It is still comparatively rare for them to survive into their thirties.

One of the tragedies of CF is that it often appears to afflict a family with no previous experience of the disease. But, in 1989, after an international quest that had continued for more than a decade, researchers in the United States and Canada identified the gene responsible for the disease.

Like all genes, it represented a recipe for cells to make a specific protein and once the researchers knew the recipe they could hunt for the protein in affected cells and try to establish its function. They discovered that the protein controls the movement of chloride (salt) ions across cell membranes, which helps to explain why people who suffer from cystic fibrosis are unable to keep the airways of their lungs wet and therefore clear.

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