Cystic fibrosis (CF), which is a hereditary
disorder, affects the exocrine glands. There is currently no cure for this
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.
1989, scientists identified that a mutation in a gene located on Chromosome 7
. 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.
The new gene
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.
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.
The Ģ3m 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
This was a Randomized Controlled Trial (RCT) to study the effectiveness of
non-viral based method on cystic fibrosis.
Out of 140 people with
cystic fibrosis, gene therapy named as pGM169/GL67A
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.
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.
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.
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
of the study
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.