Oxford
trial that improved vision in choroideremia raises hopes gene therapy may be
applied to common causes of blindness
The Guardian, Ian Sample, science correspondent, Thursday 16 January 2014
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| Robert MacLaren, consultant surgeon, warns that the trial patients' improved vision cannot yet be affirmed as permanent. Photograph: University Of Oxford/PA |
Two men
with progressive blindness have regained some of their vision after taking part
in the first clinical trial of a gene therapy for the condition.
The men
were among six patients to have experimental treatment for a rare, inherited,
disorder called choroideremia, which steadily destroys eyesight and leaves
people blind in middle age.
After therapy
to correct a faulty gene, the men could read two to four more lines on an
optician's sight chart, a dramatic improvement that has held since the doctors
treated them. One man was treated more than two years ago.
The other
four patients, who had less advanced disease and good eyesight before the
trial, had better night vision after the therapy. Poor sight in dim light is
one of the first signs of the condition.
Writing in
The Lancet , doctors describe the progress of the patients six months after the
therapy. If further trials are as effective, the team could apply for approval
for the therapy in the next five years. Some other forms of blindness could be
treated in a similar way.
Toby Stroh,
56, a solicitor from London, was in his early 20s when a consultant told him he
would be blind by the age of 50. "I said 'what do you mean?' and he said,
'you won't be able to see me'. It was a long way away, but still a bit of a
shock."
Stroh was
told later that his vision had deteriorated so much he would have to stop
driving. Then, when he joined a solicitors' firm he told a partner his eyesight
was not expected to last. The response was: "We'll be sorry to see you
go."
Stroh had
gene therapy to his left eye, the worst eye, in February 2012, and has had some
sight return to it.
"This
result does not make me swing from the chandeliers. I refuse to say everything
is going to be roses. But there is hope," he said. "For the past 30
years I've been living under the awfulness, the insidious inevitability, of
going blind, and now as a result of this work that's been done there is a very
real prospect that I will continue to be able to see, and that is just
absolutely fantastic."
Jonathan
Wyatt, 65, a barrister from Bristol, was the first patient to have the therapy.
He had hoped to spend his youth surfing around the world, but changed his mind
at the age of 20 when a consultant told him he had no idea if his vision would
last one, two or three more years.
Wyatt had
gene therapy in October 2011 and soon after was able to read the numbers on a
mobile phone for the first time in five years. "In my view my eyesight has
improved enormously since the operation."
Doctors
said the improvements in the two patients went far beyond their expectations,
but they cautioned that it was too soon to say whether the effects would last.
"It is
still too early to know if the treatment we have initiated is a permanent cure,
but so far the vision that we've seen improved has been maintained," said
Robert MacLaren, a consultant surgeon at the Oxford Eye Hospital, who led the
trial.
Choroideremia
is an X-linked disorder, meaning it is caused by a faulty gene, called CHM, on
the X chromosome. The disease mostly affects men because they have only one
copy of the X chromosome. Women have two copies of the X chromosome, so a
healthy version of the gene on one chromosome can largely make up for any
defects on the other.
The therapy
uses a genetically modified virus to smuggle healthy copies of the CHM gene
into light-sensitive cells in the retina and supporting tissue called retinal
pigment epithelium.
Surgeons
injected 10bn modified virus particles behind the retinas of the first six
patients in an operation that could be completed in an hour under general
anaesthetic.
The
injected viruses infect the eye cells, which then use the new CHM gene to correct
the choroideremia. The therapy only works on cells that have not been destroyed
by the disease. It cannot replace cells that have died off.
MacLaren
has given three more patients a higher dose of the gene therapy and hopes to
start a larger trial with about 30 people next year.
Wayne
Thompson, 43, an IT manager in Staffordshire, was treated in April 2013. His
night vision began to fail in his 20s, and over time his peripheral vision got
worse, until he began to use a white cane to get around.
"One
night in the summer my wife called me outside as it was a particularly starry
evening. As I looked up I was amazed that I was able to see a few stars. I
hadn't seen stars for a long, long, time," Thompson said. "Even if
the improvement lasts I will still be visually impaired. My life has not become
easier because of the trial, but it may have stopped it getting much, much,
harder."
The work
raises hopes for gene therapies for more common causes of blindness, such as
retinitis pigmentosa and age-related macular degeneration. Some forms of
blindness cause rapid sight loss, and are caused by multiple genes, so therapy
might need to be given in childhood and correct several genes at once.
"It's
pretty convincing that they see some functional improvement in the treated
eyes," said Hendrik Scholl, professor of ophthalmology at Johns Hopkins
University. "I find this very exciting."
But he
added that measurements of supporting tissues, called retinal pigment
epithelial cells, seemed to show that the therapy had not stopped the
degeneration of the eye completely. "The data suggest that they were able
to slow down the progression of the disease, but not stop it. But after only
six months it is very difficult to draw any conclusions."
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