Cystic fibrosis gene therapy shows promise in trial

3 Jul

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.

inhaling gene therapy
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

therapy, and:

“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

the effect.”

“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