James Bainbridge, UCL
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Kat:: Over recent decades, the scientific world has become increasingly excited about the potential for gene therapy - manipulating or replacing faulty genes to treat or even cure human diseases. But so far there’s been a lot of hype, but very little actual progress in clinical trials. Now things seem to be making some headway, particularly with gene therapy for certain forms of sight loss.
To find out more I spoke to Professor James Bainbridge, from UCL’s Institute of Ophthalmology, who’s testing treatments that deliver genes directly to the retina - the area at the back of the eye responsible for vision. I started by asking him to explain exactly what we mean when we talk about gene therapy.
James:: So gene therapy refers to treating someone’s condition at a genetic level. Perhaps the simplest form, it involves using a gene to treat a condition. That gene is typically one that the patient, the person with the condition, otherwise lacks. So, some people develop conditions because they fail to inherit a critical gene from either of their parents and the simplest of gene therapy involved providing them with a copy that they would otherwise have inherited from their parents.
Kat:: In the case of the area that you're interested – the eyes – what kind of conditions are we talking about where you think gene therapy could be a promising avenue? Are we talking about very common or quite rare diseases? What kinds of diseases are they? Can you give me some examples?
James:: These diseases which are inherited are cumulatively quite uncommon. In fact, they are a significant cause of sight loss in the UK. They comprise a large number of distinct conditions, all associated with specific defects in different genes and so, one of the challenges that we face is being able to develop treatments that are going to address each and every one.
Kat:: So individually, they could be quite rare, but together, a large number of people are affected.
James:: That’s exactly right.
Kat:: So, how do you actually do gene therapy on someone’s eyes, on their eyesight?
James:: So, the aim is to provide the cells in the retina with the genes that they otherwise lack. To do that, we can use microsurgery to inject the genes into the retina. To improve the efficiency of that, we can package the genes within a modified virus or a vector. Using some of the modern vectors that have been developed, we can do so very efficiently. And in some of the models, we are confident that the genes are seen to be preserved in the eye for many, many years.
Kat:: So basically, you're injecting viruses carrying replacement genes into the back of someone’s eyeball. Is it working?
James: We’re very excited to see actually that it does appear to work. In some very carefully selected conditions, using some very carefully developed bespoke techniques, we’re very confident that this particular technique can offer benefit in terms of improving aspects of sight in people who otherwise lack it. The challenge now, were going to be to address a number of different conditions and try to expand the potential application of this to a larger number of people.
Kat:: It is quite easy to see how this could be a really great approach for conditions that are caused by a single gene fault. What about more complex conditions of sight loss that might involve multiple gene faults or just slow degradation of your vision over time?
James:: So certainly, it’s going to be much less straightforward to target multifactorial or multi-genetic conditions. Although there are some distinct advantages to using this kind of technology for such conditions in the eye because gene therapy technology which involves delivering a gene into the eye in a stable way is one way of establishing delivery of a therapeutic protein of a medicine to the eye locally in a targeted and sustained way so that people will potentially expect to benefit over a long period of time. There are a number of applications at the moment for repeated injections of medicines into the eye and this potentially offers one alternative to that.
Kat:: In terms of where we are with this kind of approach, how close are we to seeing this in the clinic or in a more widespread level or is it still really at an experimental stage?
James:: At the moment, this is very much at the experimental stage. We are addressing a number of different conditions in the clinic. A number of different patients and people with inherited sight disorders particularly, but also those with more common conditions such as age related macular generation are participating in clinical trials of this very novel technology. We’re very excited by the first results that suggest that it can be safe and that people can benefit, but it's too early to say at the moment how much we can expect to benefit and for how long in the longer term.
Kat:: In terms of the trials that have been done, have there been some examples where you’ve just gone, wow! For example, someone really has seen a massive benefit?
James:: Absolutely - we’re very excited. In our own trial of gene therapy for a form of childhood blindness that a number of individual’s natural number of children have actually been able to benefit by improved night vision and it’s fantastic to see that response.
Kat:: It must be really lovely when you think, “Actually, I've changed this kid’s life.”
James:: We have a number of examples. One specifically is a boy who is 8 years old, who typically and before his involvement in the trial, struggled to socialise during the winter months because of his night blindness. And so, he would prefer not to go outside and not to socialise or play football at dusk or in the dark. It’s been very exciting to see how his social life have been transformed if you like by the ability to play football outside in the evening. And that sort of thing is really very rewarding. It’s certainly very exciting. It’s just too early to know how soon this might be applicable to other people who have similar disorders. We’re very optimistic for the future.
Kat:: That was Professor James Bainbridge from UCL.