Gene therapy for cystic fibrosis shows encouraging results | University of Oxford
Patients who received therapy showed a significant but modest benefit in lung function compared with those receiving a placebo.
Patients who received therapy showed a significant but modest benefit in lung function compared with those receiving a placebo.

Credit: Shutterstock/Andrey Popov. This image comes from Shutterstock.

Gene therapy for cystic fibrosis shows encouraging results

A therapy that replaces the faulty gene responsible for cystic fibrosis in patients' lungs has produced encouraging results in a major UK trial.

The study was carried out by the UK Cystic Fibrosis Gene Therapy Consortium, a group of scientists and clinical teams from Imperial College London, the Universities of Oxford and Edinburgh. It involved 116 patients aged 12 and over who received monthly doses of either the therapy or the placebo for one year.

Patients who received therapy showed a significant but modest benefit in lung function compared with those receiving a placebo. The trial is the first to show that repeated doses of gene therapy can have a meaningful effect on the disease, and change the lung function of patients. However, the team say more research is needed to improve the effectiveness before the therapy will be suitable for clinical use.

Cystic fibrosis (CF) is the commonest lethal inherited disease in the UK, affecting around 10,000 people nationally and over 90,000 worldwide. Patients' lungs become filled with thick sticky mucus and they are vulnerable to recurrent chest infections, which eventually destroy the lungs.

The trial, conducted in London and Edinburgh, compared the effects of inhaled gene therapy and a placebo on patients with CF aged 12 and over. Lung function was assessed using a common method of measuring the volume of air a patient can forcibly exhale in one second. Over the course of a year, patients were given 12 treatments at monthly intervals. The results, published in The Lancet Respiratory Medicine, showed that at the end of the trial lung function was 3.7% better in patients who received the 'active' treatment. Participants with the worst lung function at the start of the study experienced a much greater 6.4% gain compared with those in the placebo group.

Professor Deborah Gill of Oxford University's Radcliffe Department of Medicine said: 'This clinical trial is the first time that gene therapy has been shown to have a significant benefit in lung function. We have spent several years working to improve the gene therapy – specifically the plasmid molecule carrying the gene – to make sure the beneficial effects could last a long time, rather than only the few days that had been observed in earlier trials.

'Whist these results are promising, the gene therapy is not ready to give to patients tomorrow. While on average patient lung function improved measurably, some patients did not notice any benefit from the treatments, so we need a follow-on study. We only delivered 5ml – about a teaspoon – of the gene therapy sprayed into the lungs once a month. In follow on trials we would like to deliver more gene therapy at more frequent intervals to see greater effects.'

The cause of CF, mutations in a gene located on chromosome 7, was identified in 1989, opening the door to introducing a normal copy of this gene using gene therapy. In the latest trial, patients were treated by inhaling molecules of DNA wrapped in fat globules (liposomes) that deliver the gene into the cells in the lung lining.

Ed Owen, Chief Executive of the Cystic Fibrosis Trust, said: 'The results of this pioneering clinical trial are promising and suggest that it is possible to slow the decline of lung function in cystic fibrosis patients. Further clinical research is now needed to confirm the safety and efficacy of gene therapy.

'The Gene Therapy Consortium has been supported by the cystic fibrosis community for over 12 years and the Cystic Fibrosis Trust is proud to have funded the initial programmes that led to the largest worldwide gene therapy trial.'

The current trial is funded by a partnership between the National Institute for Health Research (NIHR) and the Medical Research Council (MRC). The consortium is developing a second therapy that uses a virus to deliver the DNA into cells. They are aiming to begin the first clinical trial of this treatment in 2016.