Results are promising from the first clinical trial of a gene
therapy for an inherited cause of progressive blindness called
choroideremia.
The phase I clinical trial is funded by the Health Innovation
Challenge Fund, a partnership between the Wellcome Trust and the
Department of Health.
The aim of the treatment in this study was to get the gene
therapy into the cells in the retina of the eye without causing
damage. After six months, however, the patients actually showed
improvements in their vision in dim light and two of the six were
able to read more lines on the eye chart.
A total of nine patients have now had one eye treated with the
gene therapy in operations at the Oxford Eye Hospital, part of the
Oxford University Hospitals NHS Trust. The therapy is given in one
eye to allow comparison with progression of the disease in the
other eye.
Results at six months are reported for the first six patients.
The first patient to receive the operation has now been followed up
for over two years. Based on the success of the treatment in the
first six patients, three more have recently been tested at a
higher dose.
Professor Robert MacLaren of the Nuffield Laboratory of
Ophthalmology at the University of Oxford, and a consultant surgeon
at the Oxford Eye Hospital and honorary consultant at Moorfields
Eye Hospital, led the development of the retinal gene therapy and
this first clinical trial. He says: "It is still too early to know
if the gene therapy treatment will last indefinitely, but we can
say that the vision improvements have been maintained for as long
as we have been following up the patients, which is two years in
one case.
"The results showing improvement in vision in the first six
patients confirm that the virus can deliver its DNA payload without
causing significant damage to the retina. This has huge
implications for anyone with a genetic retinal disease such as
age-related macular degeneration or retinitis pigmentosa, because
it has for the first time shown that gene therapy can be applied
safely before the onset of vision loss."
The first patient to be treated, Jonathan Wyatt, 65, says: "My
left eye, which had always been the weaker one, was that which was
treated as part of this trial… Now when I watch a football match on
the TV, if I look at the screen with my left eye alone, it is as if
someone has switched on the floodlights. The green of the pitch is
brighter, and the numbers on the shirts are much clearer."
Choroideremia is a rare inherited cause of blindness that
affects around one in 50,000 people. The first signs tend to be
seen in boys in late childhood, with the disease slowly progressing
until vision is lost. There is currently no cure. It is caused by
defects in the CHM gene on the X chromosome, which explains why it
is almost always males who are affected. Without the protein
produced by the CHM gene, pigment cells in the retina slowly stop
working, then die off. As the disease progresses, the surviving
retina gradually shrinks, reducing vision.
The gene therapy approach developed by Professor MacLaren's team
uses a small, safe virus to carry the missing CHM gene into the
light-sensing cells in the retina. In an operation similar to
cataract surgery, the patient's retina is first detached and then
the virus is injected underneath using a very fine needle. The aim
is for the CHM gene, once delivered into the cells of the retina,
to start producing protein and stop the cells dying off.
This is the first time that a gene therapy has targeted the
principal light-sensing cells in the retina, known as
photoreceptors. This means the approach has relevance for other,
far more common causes of blindness in which these light-sensing
cells are affected, such as retinitis pigmentosa and age-related
macular degeneration.
Wayne Thompson, 43, an IT project manager in Staffordshire, was
treated in April with a higher gene therapy dose as part of the
subsequent trial: "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... For a long time I lived with the certainty
of losing vision. Now I have uncertainty of whether the trial will
work, but it is worth the risk."
Dr. Ted Bianco, Director of Technology Transfer at the Wellcome
Trust said: "Whilst it is important to recognise that it is early
days in assessing this new treatment, it is good to see the
encouraging results of this trial to find safe and effective
approaches to patient care based on gene therapy. Pioneering work
like this helps lay down the foundations for a wide array of
potential, future treatments of people living with genetic
disorders."
The research has received additional support from the National
Institute for Health Research Oxford Biomedical Research Centre and
the charity Fight for Sight, the main UK charity that funds
pioneering eye research to prevent sight loss and treat eye
disease.
The paper, Retinal gene therapy in patients with
choroideremia: initial findings from a phase 1/2 clinical
trial, is published in the Lancet.