The largest trial for a gene therapy for cystic fibrosis (CF) will begin in the UK this month. Coordinated by the UK Cystic Fibrosis Gene Therapy Consortium (GTC), 130 patients will be recruited and given working copies of the defective gene that leads to their condition.
Mutations in this gene, called CFTR, cause patients' lungs to become filled with mucus, making them vulnerable to frequent chest infections and reducing their average lifespan to 35 years. As the commonest lethal inherited disease in the UK it affects 9,000 people, and over 90,000 worldwide.
Although the genetic cause has been known since 1989, there is still no cure, as it has been difficult to develop effective gene therapies that deliver the working gene directly to the lungs. As Professor Eric Alton from Imperial College London, who coordinates the GTC, told Radio 4's Today programme, his team has spent the last decade trying to find 'tricks to slip the gene in'.
Participants in the new study will receive the treatment over the course of a year using a nebulizer — a device similar to an asthma inhaler — to inhale molecules of DNA that contain the replacement gene.
Previous GTC trials have shown that the inhalation method can successfully introduce the new gene and that its effect lasts for up to a few months. The next step is to discover whether repeated exposure leads to improved lung function, and to reductions in mucus, inflammation and infection.
'No one has ever done a gene therapy study like this in cystic fibrosis before', said Dr Deborah Gill of the Nuffield Department of Clinical Laboratory Sciences at Oxford University, one of the institutes involved in the research. 'By giving the therapy over a whole year, we will have the best chance yet of seeing an improvement in patients'.
It is hoped that the trial, made possible by a £3.1 million grant from the National Institute for Health Research and the UK Medical Research Council (MRC), will lead to successful treatments, and ultimately a cure, for CF.
Professor Alton expressed hope that the new therapy 'will achieve a step change in the treatment of cystic fibrosis that focuses on the basic defect rather than just addressing the symptoms'.
While he urged caution, telling the Today programme that the science needed to be 'built up gradually', he added that if it works the researchers could 'book their tickets to Stockholm to pick up their Nobel Prize'.
Additional lab-based studies by the GTC that look into more effective gene therapy delivery methods will also be funded by the MRC.
The GTC comprises a team of clinicians and scientists from Imperial College London, the Universities of Oxford and Edinburgh, Royal Brompton and Harefield NHS Foundation and NHS Lothian. The outcome of the phase two trial will be known in Spring 2014, and regular updates will be posted on the GTC website.