The results of a trial provide the first proof of concept that non-viral gene
therapy is safe and can benefit lung function in patients with cystic fibrosis, say
investigators writing in The Lancet Respiratory Medicine.
Trial participants receive the gene therapy by inhaling fat globules containing the corrective DNA.
Image credit: Imperial College London
The trial – run by the UK Cystic Fibrosis Gene Therapy Consortium – now needs to be followed
by further studies to assess the optimum dose and treatment schedule, they add.
The placebo-controlled, double-blind trial was carried out at two centers in the UK and
recruited 136 cystic fibrosis patients over the age of 12.
The patients received either monthly doses of the gene therapy or a placebo for 1 year.
The trial tested a gene therapy where the patient inhales molecules of DNA wrapped in fat
globules (liposomes) that deliver a correct copy of the gene into the cells in the lung
Cystic fibrosis is a condition where the lungs produce too much thick mucus, making
breathing difficult and increasing the risk of infection.
The disease is caused by a single faulty gene located on chromosome 7.
Gene therapy shows ‘significant but modest’ benefit
After 1 year of treatment, compared with placebo, patients who received the gene therapy
showed “a significant,
albeit modest, benefit” in forced expiratory volume or FEV in 1 second (a measure of lung function), write
the study investigators, who note that such a result indicates a “stabilization of lung
function in the treatment group.”
They conclude the trial is the first to show that repeated doses of gene therapy can
have a meaningful effect on cystic fibrosis and change lung function.
However, they warn there is still some work to do before the treatment is ready for clinical
use. The effectiveness needs to be improved and the correct dosing needs to be established.
Lead author Eric Alton, a professor of gene therapy and respiratory medicine at Imperial
College London, and consultant physician at Royal Brompton Hospital, is the coordinator of the
Consortium. He adds that the findings also showed there were no safety concerns about the
“Whilst the effect was inconsistent, with some patients responding better than others, the
results are encouraging, laying the groundwork for further trials, which we hope could improve
“We are looking to undertake follow-up studies assessing higher, more frequent doses as well
as combinations with other treatments,” he adds.
‘Step change’ in treatment of cystic fibrosis
Prof. Alton explains that by focusing on the basic defect underlying the disease rather than
just its symptoms, they aim to bring about a “step change” in the treatment of cystic
“It has taken more than 20 years to get where we are now, and there is still
some way to go. Eventually we hope gene therapy will push CF patients towards a normal life
expectancy and improve their quality of life significantly.”
Funding for the trial came from a partnership between the Medical Research Council (MRC) and
the National Institute for Health Research (NIHR).
The Consortium is also developing a second therapy that uses a virus to deliver the
corrective DNA to the lung cells. First clinical trials are expected to start in 2016.
Publication of the trial results follows other welcoming news that Medical News
Today reported recently of a new drug combination that targets the most common genetic
cause of the disease could extend the life of cystic fibrosis
The trial results showed that treatment with a combination of lumacaftor and ivacaftor led
to a reduction in required hospital antibiotic courses, and other improvements.
Written by Catharine Paddock PhD