Scientists have improved the vision
of a small number of patients suffering
from a rare and incurable
eye disease by replacing a defective
gene with a healthy
one-a boost for a technique
known as gene therapy.
英国牛津大学(University of Oxford)眼科学教授、上述临床试验的负责人麦克拉伦(Robert MacLaren)称，病人视力的改善程度出乎意料。
The patients have choroideremia, a degenerative disease caused by defects in a single gene that leads to blindness
and affects 1 in 50,000 people. In an early-stage trial published Wednesday in the Lancet, the researchers used a deactivated virus to safely
ferry billions of healthy, lab-made versions of the gene into the retina. That appeared to restore
of light-sensitive cells, which the disease impairs.
'We were surprised by the magnitude
improvement' in the patients, said Robert MacLaren, a professor of ophthalmology at the University of Oxford in England and leader of the clinical trial.
The experiment marks one of the first times that gene therapy has targeted the main light-sensing cells in the retina. It thus offers a possible route for treating far more common causes of blindness
the same cells, such as retinitis pigmentosa and age-related macular degeneration.
Gene therapy involves the use of DNA, rather than a protein
or drug, to treat an ailment. The idea is that if the DNA gets properly
embedded in the target cells, it can potentially remain there indefinitely
and deliver benefits for a long time.
Gene therapy fell out of favor after a handful
of early studies led to cancer
and death. That's a big reason why it hasn't yet led to a single authorized treatment
in the U.S.
Now, the technique
is making a comeback. For example, in three early-stage clinical trials done a few years ago, the technique
was used against a retinal disease called Leber congenital amaurosis. And in November 2012, European regulators approved a gene therapy treatment
for a rare condition that leaves patients unable
fats-the first such approval
in the Western world.
treated in the Lancet study, choroideremia, is caused by defects in a single gene on the X chromosome and mainly
affects boys. Many start losing night vision
by age 10 and become legally
blind in their 40s.
Because of the defective
gene, light-sensitive cells in the retina slowly stop working
and then die. Prof. MacLaren's team decided
to make healthy
versions of the gene in the lab, load each onto a small virus (one that doesn't cause disease in people) and inject
the mix under the retina.
The therapy is given in one eye so it's easy to compare the progression of the disease with the untreated eye. 'Every injection has 10 billion
viral particles, each carrying one copy of the gene,' said Prof. MacLaren. 'We have to target millions of cells.'
The trial began with six patients. Two still had excellent visual acuity-clearness of vision-which is measured by reading
lines of letters on a sight chart. Two other patients had good acuity and two had reduced acuity.
Six months after the operation, the two patients with reduced acuity showed improved vision, being able to read two and four more lines on the sight chart. The others could see better in dim light. The gains were sustained over several months of follow-up.
A 65-year-old in the trial said that when he now watches a soccer game on TV the 'green of the pitch is brighter and the numbers on the shirt much clearer.' Another who went through the procedure
says he can now see stars in the night sky, which he hadn't seen for a long time.
Altering a patient's DNA is risky because it can trigger
dangerous side-effects. In this case, there was no sign of an immune reaction
in the first six months of the follow-up, according to the Lancet study.
The scientists hope to treat patients before their sight falters. 'We want to preserve
they've got,' said Prof. MacLaren. He now plans to test the technique
on a larger group of about 30 patients.