Gene therapy for blindness (2012)

[Robert MacLaren:] We have, in the laboratory here, developed a new treatment involving gene therapy, which is new technology being developed in medicine. We are treating a disease called choroideremia. This disease affects young men. It presents in childhood
and it causes progressive loss of sight and eventual blindness
by the time the patients are in their 40s. The disease was first described
over 100 years ago in 1872, and there are lots of patients affected by it worldwide. The disease is caused by a missing gene. (A gene is a part of the DNA — the code that we
have in our bodies to make cells work correctly.) The DNA is missing a certain gene known as REP1, and that gene is on the X chromosome, which is one of the parts
of the DNA in all cells in the body. Because it’s on the X chromosome, the disease
effects meant it primarily causes sight-loss in men and presents in childhood. Gene therapy is a technique we use
where we artificially make the missing gene and we use a virus to put it back into the cells that need the gene in order to survive. In the case of the retina
(the lining of the back of the eye), these patients are going
blind because the cells are degenerating. So what we plan to do,
and what we are doing in this clinical trial, is we are injecting the gene back into the cells, and we’re using the virus to
carry the gene, to infect the gene into the cells and hopefully preserve vision
in patients who have got this terrible disease. Choroideremia affects about 1 in 50,000 people, so that is a fairly rare disease, but it’s prevalent worldwide. So in the UK there may be 1,000 people affected, worldwide there may be 100,000, possibly more because in
many countries the disease is underreported. What’s unique about it, is that
it’s instantly recognisable to most eye specialists. If we can look into the back of the eye and we can see a disease
where we know the genetic cause by its appearance, it’s much easier to develop a gene therapy treatment. Because we can instantly collect a load of patients without needing to do complicated genetic testing — we can see
what the disease is at the very beginning. So far, we have treated 6 patients but we have approval to treat a further 6, which we’ll be doing later this year. The preliminary results of the study are very promising but any primary study on something new like this is designed around safety first of all. Once we’re happy that the treatment is safe,
then we can expand the trial to include more people and look at more
complicated outcomes of their vision. The period in which
we’re actually treating the patients is one year and then we follow them up for two
years because the degeneration is quite slow, so we won’t necessarily know instantly if it’s worked. We need to wait a couple of years in which we can compare the rate of degeneration in the treated eye to the degeneration in the untreated eye, like a control. We estimate, by looking at
the data on the rate of degeneration, that we’ll know within two years
if we’ve been successful in stopping it. We engineered a viral vector which we designed in our
laboratories and tested in the University of Oxford. The vector which we designed has to be made in a certain way to enable it to be injected into patients. Obviously, you can’t just inject viruses into patients because there could be some toxic effects. We’re very fortunate here in Oxford
that we have a clinical bio-manufacturing facility, which is approved by the Medicines and Healthcare Products Regulation Authority, the MHRA in the UK, which allows us to bring in, store and
develop these very complicated gene therapy products in a way that wouldn’t be available in many other academic centres in the UK.

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