Gene Therapy for Cystic Fibrosis Shows Some Promise in Study

Lung function benefit was slight, but even keeping lungs stable would be improvement, experts say

By Mary Elizabeth Dallas

Thursday, July 2, 2015

THURSDAY, July 2, 2015 (HealthDay News) -- Gene therapy for cystic fibrosis has for the first time shown slight but significant benefit on lung function, new British research reveals.

In a randomized trial, patients inhaled molecules of DNA that aimed to replace the defective gene responsible for cystic fibrosis with a healthy, working copy of the gene in the lungs.

"Patients who received the gene therapy showed a significant, if modest, benefit in tests of lung function compared with the placebo group, and there were no safety concerns," study senior author Eric Alton of the National Heart and Lung Institute at Imperial College London, said in a news release fromThe Lancet Respiratory Medicine, which published the study.

Even though the effect was "inconsistent, with some patients responding better than others, the results are encouraging," Alton said.

Cystic fibrosis is a rare, inherited respiratory disease that is caused by mutations in a gene called cystic fibrosis transmembrane conductance regulator, (CFTR). The condition affects more than 90,000 people around the world.

Scientists working to develop treatments for cystic fibrosis have identified some 2,000 mutations to the CFTR gene, which can cause the lining of the lungs to ooze very thick mucus. This results in serious and recurring lung infections that damage the lungs and cause the vast majority of deaths among those with the disease, the researchers explained.

A variety of methods have been developed to deliver a normal CFTR gene into the lungs, but no therapy to date has been able to show long-term improvements.

The two-year study involved 136 British cystic fibrosis patients aged 12 or older. Over the course of one year, these patients were randomly assigned to receive either the gene therapy or a "dummy" saline placebo at monthly intervals.

Alton's team evaluated their lung function by measuring the volume of air forcibly exhaled in one second, known by the abbreviation FEV1.

After one year of treatment, the measure of lung function, or FEV1, of the patients who received the gene therapy was 3.7 percent greater than those who received the placebo, the study found. The team stressed that response appeared to be due to a stabilization of lung function -- not actual improvement.

However, "stabilization of lung disease in itself is a worthwhile goal," study senior co-author Stephen Hyde, from the Gene Medicine Research Group at the University of Oxford, said in the news release.

"We are actively pursuing further studies of nonviral gene therapy looking at different doses and combinations with other treatments, and more efficient vectors," he added.

The study also showed that some patients respond better to the therapy than others. Those with the worse lung function when the study began saw twice the benefit, the researchers noted.

The gene therapy was generally well-tolerated in patients on the treatment, with negative reactions being similar to that seen in people taking the placebo.

One expert in the United States was encouraged by the findings.

"In order to get the 'normal' gene into the lung, it has to be connected to something called a vector," explained Dr. Joan Decelie-Germana, of the division of pulmonary medicine & Cystic Fibrosis Center at Cohn Children's Medical Center in Great Neck, N.Y.

"In this study, the vector is a nonviral vector combination that has been shown to be safe in earlier studies," she said.

The new results are encouraging, but the therapy should be tried "in a larger study including more patients, to see if these results are reproducible in many more patients," Decelie-Germana stressed. "It will also be important to study this gene therapy in other countries, since different patients are known to have different gene mutations."

SOURCES: Joan K. Decelie-Germana, M.D., department of pediatrics, Division of Pulmonary Medicine & Cystic Fibrosis Center, Cohen Children's Medical Center, Great Neck, N.Y.; The Lancet Respiratory Medicine, news release, July 2, 2015

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