A treatment to help those with cystic fibrosis may be available within five years, say scientists who who have been working for decades to develop a gene therapy for the disease.

The results of a year-long trial showed only a small and variable improvement in the lung capacity of those children and adults who took part, but scientists now believe they have proved gene therapy is possible in treating cystic fibrosis. With more work, they say that by the end of the decade it will at least be possible to help stabilise patients.

Cystic fibrosis, the most common life-shortening inherited disease in the UK, was an early target for scientists excited by the concept of gene therapy when the mutated gene that causes it was identified some 25 years ago.

It is the world’s first demonstration that repeated gene therapy can improve lung function Professor Eric Alton

It is estimated that one in every 2,500 babies born in the UK will be born with cystic fibrosis, with the disease affecting about 10,000 people in the UK, and more than 90,000 worldwide. Those born with CF have a limited lifespan. Their body produces thick mucus, which affects the lungs and digestive system in particular.

Scientists and doctors from Imperial College London, Oxford and Edinburgh Universities, the Royal Brompton & Harefield NHS Foundation Trust, and NHS Lothian came together in 2001 to try to develop a gene therapy, supported by the Cystic Fibrosis Trust. They developed a technique to enable patients to breathe in molecules of DNA, delivering a normal copy of the defective gene to cells in the lung.



A trial of 136 patients, aged 12 and over, showed better lung function in most of those given gene therapy. “It is the world’s first demonstration that repeated gene therapy can improve lung function,” said Professor Eric Alton, the coordinator of the UK Cystic Fibrosis Gene Therapy Consortium from Imperial. But he said: “The effects were modest and variable. This is not yet ready for clinical use for those reasons.”

Half the patients treated at the Royal Brompton and at Western General hospital in Edinburgh were given the gene therapy and half given saline instead. Those who did best were those with the worst lung function. Alton explained that mucus was obstructing their smaller airways, so that most of the dose ended up in the larger airways. For those with milder respiratory problems, “we’re simply going to have to increase the dose,” he said.

The scientists have not found a way to make a permanent change to the faulty gene. In the trial, published in the journal Lancet Respiratory Medicine they dosed patients once a month. Dosing them more often could improve the results, they say. In a bigger trial, they will also try combining the gene therapy with other treatments.

A second new trial is planned that will deliver the therapy through a specially engineered virus rather than encasing it in fat globules – the method used to date – which might give longer term benefits. Giving repeated doses via a virus is not usually possible, because the immune system recognises and rejects it.

If the next trial shows a bigger benefit, said Alton, it would be feasible to have a treatment to improve lung function available for patients by the end of the decade. The aim would be to prevent damage to the lungs occurring.

Developing a gene therapy for cystic fibrosis has proved to be much more difficult than anybody imagined 25 years ago. “The lungs must be one of the worst possible organs to go for,” said Alton. “They are so extremely well-defended. With bone marrow you can take it out, do the gene transfer in controlled conditions in the laboratory and put it back in the patient. That is the low-hanging fruit. We have gone for the high-hanging fruit but I’m not at all sorry we have.”

Gene therapy remains largely an experimental technique, with some treatments available mostly for rare diseases. The aim has been to effect a cure, but the benefits have generally not been as long-lasting as hoped.

The cystic fibrosis trial was funded by the Medical Research Council and the National Institute for Health Research. Pledging to continue investment in health research, George Freeman, the government’s minister for life sciences, said: “Cystic fibrosis can have a devastating effect on patients and families and this is an excellent development for people living with the condition.”

Ed Owen, chief executive of the Cystic Fibrosis Trust, said: “This is an extraordinary time for therapeutic development in cystic fibrosis and the need is urgent to stop so many young lives being cut short because of this cruel condition. We will therefore continue to invest in innovative genetic research and to work with academic and industry partners to develop advancements which will make further progress towards our goal of a life unlimited by cystic fibrosis.”