Gene Therapy Offers Hope to Cystic Fibrosis Patients After Successful Trials

Cystic fibrosis (CF), which is a hereditary disorder, affects the exocrine glands. There is currently no cure for this disease. Cystic fibrosis causes production of thick sticky mucus that blocks the bronchi, often resulting in recurrent lung infections. Currently the median predicted survival age for cystic fibrosis is about 40 years.

In 1989, scientists identified that a mutation in a gene located on Chromosome 7 caused cystic fibrosis. The gene associated with cystic fibrosis was named as CFTR gene. For more than 20 years, many scientists have done several researches on the cystic fibrosis gene. But for the very first time scientists in Britain have found that correcting the defective gene associated with cystic fibrosis by therapy can yield positive results.

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The new gene therapy has offered a significant improvement among children suffering from this respiratory disease. This treatment repairs the faulty CFTR gene by adding a healthy gene over it. Currently, this breakthrough has given new hope for developing life-saving treatments for individuals with cystic fibrosis.

The clinical trial which involved 136 patients, was carried out by Dr. Eric Alton, the co-ordinator of the UK consortium of universities and hospitals. The trial - demonstrated that the monthly dose of gene therapy over a course of a year can alter the lung function without any harmful side-effects.

Study Highlights

The £3m Phase-2 trial was conducted at the Royal Brompton Hospital in London and the Western General Hospital in Edinburgh. All patients were over the age 12 with lung function between 50-90% of normal individuals. The patients’ lung function was measured using a standard test called Forced Expiratory Volume in 1 second (FEV1). This was a Randomized Controlled Trial (RCT) to study the effectiveness of non-viral based method on cystic fibrosis.

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Out of 140 people with cystic fibrosis, gene therapy named as pGM169/GL67A was given to 78 patients and placebo to 62 patients. About 5ml of pGM169/GL67A containing 13.3mg of plasmid DNA and 75mg of the GL67A lipid mixture were given to the trial group and 5ml of inactive saline was given to the placebo group. They received either treatment or placebo at 28-day intervals for 12 months. Patients in both groups also received an average of three courses of oral or intravenous antibiotics during the trial.

The patients were given a nebulising spray containing fatty droplets or “liposomes” wrapped around a synthetic copy of the cystic fibrosis gene. When these liposomes were sprayed, they got absorbed by the cells on the airway linings. After getting absorbed this gene stimulated the production of healthy proteins in the cell membranes, which prevented the lungs from getting clogged with the sticky mucus.

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The scientists found a 5% percent improvement in lung function among the treated patients and a 6% increase in the worst-affected group. Since the effect was inconsistent in the phase-2 trial, the scientists believe that further improvements in efficacy and consistency of the response to the current formulation or its combination with CFTR potentiators would be needed.

“Patients who received the gene therapy showed a significant, if modest, benefit in tests of lung function compared with the placebo group; there were no safety concerns,” said Professor Alton.

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Cystic fibrosis affects about 10,000 people in Britain and nearly 90,000 people worldwide. Current treatments for cystic fibrosis include enzymes, proteins, or salt solutions that are inhaled through nebulisers to clear mucus from the lungs. Among raising expectations for a cure, the UK consortium believes that this clinical trial acts as an initial breakthrough for undergoing further tests to develop a better gene-therapy treatment.

“The phase-3 trial will focus on increasing the liposome dose and to develop a parallel treatment involving a hybrid virus that will be able to insert the healthy copy of the gene directly into the chromosomes of the affected lung cells,” said Alton.

They also believed that the gene therapy will push CF patients towards a normal life expectancy and improve their quality of life significantly. Previous studies were conducted using virus but it was shown to be ineffective. This study is a non-virus based method where only bubbles of fat were used to deliver the gene. Also, this study is a double-blind clinical trial where both the patients and scientists were unaware of who was getting the gene treatment or the placebo.

Limitations of the study

Patients recruited in this trial were clinically stable which means they were at their optimum respiratory health during the study. Therefore, it is not known how the treatment would work in clinically unstable or very severe patient groups.
Only 140 patients were included in this study, which was a relatively small number. To fully assess the effects of this treatment, large clinical trials are needed.

The results of the phase-2 trial have been published in the journal The Lancet Respiratory Medicine. This clinical trial was done by scientists from the universities of Oxford, Edinburgh and Imperial College London.

References:

1. http://www.independent.co.uk/news/science/gene-therapy-offers-hope-to-cystic-fibrosis-patients-after-successful-trials-10361634.ht

2. http://www.nhs.uk/news/2015/07July/Pages/Gene-therapy-breakthrough-for-cystic-fibrosis.aspx

Source-Medindia