Hopes rise of therapy for cystic fibrosis: Researchers in US demonstrate that gene treatment can correct disorder

Steve Connor
Saturday 16 October 1993 00:02

THE FIRST evidence that the revolutionary technique of gene therapy works on humans with cystic fibrosis - the most common inherited disorder of northern Europeans - has emerged from research in the United States.

Scientists reported at a conference this week in Dallas, Texas, that they have successfully treated cystic fibrosis patients using gene therapy, where healthy versions of a defective gene are inserted into human tissue.

They emphasised that the research, which will be published in full next week, is still only preliminary and so far they have only demonstrated that it works on the noses of three patients.

In order for cystic fibrosis patients to benefit, gene therapy must work in their lungs, which become clogged with sticky mucus because of a defective gene that prevents the normal transport of chloride in and out of the cells lining the respiratory system.

Michael Welsh and colleagues from the Howard Hughes Medical Institute at the University of Iowa presented the results at the North American Cystic Fibrosis Conference. Further details will be published in the scientific journal Cell.

'I'm cautiously hopeful,' Dr Welsh said. ''But I think many more questions need to be answered. The really, really important issue is safety.'

The researchers sprayed the noses of their patients with the common cold virus, which they had genetically engineered to carry the normal version of the cystic fibrosis gene into defective cells. Dr Welsh found the inserted gene worked and the chloride defect was corrected.

However, large doses of the genetically altered virus will be needed in order to infect the cells lining the lungs, which may result in side-effects not seen in the three patients who received lower doses.

Nevertheless, Robert Beall of the US Cystic Fibrosis Foundation, said: ''I think it's a major milestone. We have to be very encouraged about this.'

Duncan Geddes, director of respiratory medicine at the National Heart and Lung Hospital in London, which began gene therapy trials on cystic fibrosis patients last August, said: 'This is an important first step on the long road towards gene therapy.'

His team is attempting to inject genes using fatty droplets, called liposomes, rather than viruses. A group of nine patients - all men - are taking part in the British trial. Three will receive a placebo, and six will receive liposomes carrying the gene.

A spokeswoman for the Cystic Fibrosis Research Trust in Britain said results of the trial were expected before the end of the year.

If gene therapy proves to work in the lungs of patients, it will have to be repeated on a regular basis because the respiratory system is constantly renewing the cells lining the lungs. Dr Geddes said the unanswered questions were how big the gene therapy doses will need to be, and how often they will have to be applied.

There are about 7,000 people, mostly children, suffering from cystic fibrosis in Britain. They are prone to recurrent lung infections that can lead to respiratory failure. Although antibiotics can prolong life expectancy, there is no cure for the disorder and many patients die in childhood.

The virus used in Dr Welsh's experiments was constructed by scientists at Genzyme, a biotechnology company based in Framingham, Massachusetts.

Two other US research teams - headed by Ronald Crystal, of Cornell University, and James Wilson, of the University of Pennsylvania - are conducting similar experiments. They are administering gene-carrying viruses directly to the lungs.

'They should be congratulated. It's great,' Dr Wilson said of the Iowa group's findings. He has so far treated two patients but not released any results.

However, he and Dr Crystal warned that much more work needs to be done.

Dr Crystal, who has treated three patients, said: 'It's a demonstration that you can correct the abnormality in the nose, but the disease is not in the nose.'

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