For first time, gene therapy shows promise in cystic fibrosis

By Kate Kelland

LONDON (Reuters) – Scientists conducting a major trial of a therapy that replaces the faulty gene responsible for cystic fibrosis say the treatment has showed significant benefit for the first time in patients’ lung function.

The technique, developed with the technology commercialization firm Imperial Innovations, replaces the defective gene behind the inherited lung disease by using inhaled molecules of DNA to deliver a normal working copy of the gene to lung cells.

“Patients who received the gene therapy showed a significant, if modest, benefit in tests of lung function compared with the placebo group,” said Eric Alton, a professor at Imperial College London who led the trial.

Briefing reporters about the results, he said they were “encouraging” but cautioned that because the effect was inconsistent, with some patients responding better than others, the gene therapy was not ready for regular clinical use.

“The effects were modest and variable,” he stressed.

Cystic fibrosis is the world’s most common lethal inherited disease, affecting more than 90,000 people globally. Patients’ lungs become filled with thick sticky mucus and they are vulnerable to recurrent chest infections, which eventually destroy the lungs.

In this trial, results of which were published on Friday in The Lancet Respiratory Medicine journal, 136 CF patients aged 12 and over received monthly doses of either the gene therapy or a placebo for one year.

Patients who received therapy had significant, if modest, benefit in lung function compared with placebo, making the trial the first in the world to show that repeated doses of gene therapy can have a meaningful effect on cystic fibrosis.

Dominic Wells, a professor of translational medicine at Britain’s Royal Veterinary College who was not involved in the trial, said its findings laid “a strong foundation for the development of more potent gene transfer systems”.

In this trial, patients were treated by inhaling molecules of DNA wrapped in fat globules, or liposomes, that deliver the gene into the cells in the lung lining.

Alton said his team is now planning follow-up studies to look at whether higher, more frequent doses might have a greater benefit, and to test ways of combining the gene therapy with drug treatments to potentially boost its effect.

The team has also developed another gene therapy delivery method using a hybrid virus created in the lab by combining a so-called lentivirus with another called Sendai virus, which is known for its ability to efficiently deliver replacement genes to the intended target.

(Reporting by Kate Kelland; Editing by Mark Heinrich)