TX210114-Genetherapy
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Downloaded from www.bbc.co.uk/radio4 THE ATTACHED TRANSCRIPT WAS TYPED FROM A RECORDING AND NOT COPIED FROM AN ORIGINAL SCRIPT. BECAUSE OF THE RISK OF MISHEARING AND THE DIFFICULTY IN SOME CASES OF IDENTIFYING INDIVIDUAL SPEAKERS, THE BBC CANNOT VOUCH FOR ITS COMPLETE ACCURACY. IN TOUCH – Gene Therapy TX: 21.01.14 2040-2100 PRESENTER: PETER WHITE PRODUCER: CHERYL GABRIEL White Good evening. Tonight: gene therapy seems to have taken one step closer to restoring sight, but who for, for how many people and how soon? We’ll be asking the man who’s led recent trials. And just how many new buses are having automatic spoken messages installed? We’ll be exploring the statistics. Now as we’ve observed before on this programme there’s nothing our newspapers like more than a story of sight restored and if they can include the implication that it could affect thousands so much the better. Which is why we’ve put ourselves on miracle cure watch. So how should we regard the news that a recent set of trials, involving gene therapy, has restored a degree of sight to six patients? They’re all suffering from a rare genetic condition called Choroideraemia which tends to affect men and causes seriously deteriorating sight in middle age. Great news for them and we’re genuinely delighted for them. But as always with such advances the key question is how significant is this for those with more common forms of sight loss who hear such news items and inevitably have their hopes raised? Well the man leading the trials is Robert MacLaren, professor of ophthalmology at Oxford University and an ophthalmic surgeon. As he took brief time off from his surgery this morning I asked him to explain what these advances are likely to mean in the long run. MacLaren We really wanted to establish gene therapy as something which we can apply to the eye before vision is lost because what we’re trying to do is we’re trying to replace a missing gene to try and prevent the retina from degenerating. I think I should point out that for people who have lost sight completely once the cells have degenerated and gone then gene therapy’s not really going to be of great benefit because correcting a gene defect at that stage is too late. In that situation we need to look at some of the parallel technologies that are being developed, such as the electronic retinal implant or stem cells, which are ways of restoring vision in patients in whom the retina has degenerated. For patients, however, who perhaps have retinitis pigmentosa in their family, who have children who are affected, who have the genetic diagnosis, who know that they’re going to go blind and lose their sight this is where gene therapy, I think, has great potential. But we do need to be quite courageous in what we do and we need, I think, to cross a threshold where we actually start to treat patients before they’ve lost their vision and that means a small amount of risk with the surgery. And I think in that case as gene therapy’s developed it will be applicable to many, many more diseases apart from Choroideraemia. White How does it work Professor MacLaren, I mean how does gene therapy actually take place? MacLaren Well if a patient suffers from a genetic disease that is causing them to go blind typically they might be missing an important part of the genetic code, known as the DNA, and that missing DNA is important for cells in the eye. So the concept of gene therapy is to get the DNA that is missing into those cells. We can’t just inject it through an injection into the eye or anything like that, we actually need to use some way of getting it into the cells and to do that we use a virus. And we get the virus and we take out the DNA that’s already in the virus and we put in its place the DNA of the missing gene that we want to put into the patient. The patient then undergoes an operation, a little bit similar in many ways to a cataract operation, and we then inject the viral particles under the retina, using a very fine needle, and approximately 10 billion viral particles all go into the retina and these viral particles carry with them the missing gene. So they infect the cells of the retina and as they infect the cells they release the DNA, the virus obviously in its life form thinking that it’s releasing its own DNA for replication, in fact it’s releasing the DNA of the missing gene that these patients need. That gene then goes into the cells, becomes stabilised and gets incorporated into the DNA of the patient replacing the gene that’s missing, making the missing the protein and we hope therefore stopping the retinal degeneration. White So as far as the patient is concerned complex as the science is what just a – well for them would seem quite a simple operation? MacLaren I mean I think so, I think in terms of the actual surgery involved it’s relatively simple from the patient perspective. There are certain risks associated with detaching the retina and I wouldn’t at all claim that this is complication free – there will be complications by doing it – so there is a certain risk involved. White So if you were trying to, as it were, give us a profile of who should be hopeful – and I know that’s a difficult thing to ask but in a way it’s the key thing that people listening to this want to know – who would the people be who have most to hope for from what you’ve done? MacLaren I think there would be people who know that they have a family history of a retinal degeneration, okay, and that might be macular degeneration or it could be retinitis pigmentosa but in whom there is still some useful vision and in these patients, I think, they should be very hopeful because I think gene therapy is an ideal treatment that still needs to be developed but the major problems, I think, have now been solved and the eye and the retina, in particular, is a very, very good target – organ – for gene therapy. For people, I think, who unfortunately would not benefit from this technology are people who have already lost their vision and anyone who has a disease affecting the optic nerve, such as glaucoma or optic neuropathy or something like that, in those conditions, in those causes of sight loss, the problems associated with rewiring the nerve and reconnecting the eye are really going to be incredibly complex. So I think the people who would benefit most from gene therapy are people who have a genetic diagnosis, that they know that they’re likely to go blind in future but who still have some vision and I think gene therapy has a great deal to offer for them. White And it is reasonable for people like that – if they have some vision – to think in terms of that vision not simply being stopped from deteriorating but maybe some vision being returned? MacLaren Well yes, there is always going to be a trade-off between the function that we can bring back to the cells that are still alive against the fact that the cells that have gone can never be restored. So in most cases of retinal degeneration, of course I include all types of retinitis pigmentosa in this, the peripheral vision goes first and then gradually the sight gets more and more constricted and patients develop tunnel vision. Now in the very centre, at the very last stages, the cells are not working very well because they’re very sick and I’m sure that we can boost those cells with the gene therapy once the correct gene is in place but the cells that have already been lost unfortunately there’s nothing that’s going to bring these cells back. So I think we’d be looking at small improvements in vision, possibly in the centre, but it’s very unlikely we’d be able to bring back vision from the peripheral. White And maybe the hardest question of all – with these kind of conditions – and I know it will vary – how soon are we talking about in which we might be treating substantial numbers as opposed to trials of a few people? MacLaren Well that’s a very good question. The approach that we have is that we want to focus on one disease because we want to choose what we think is the easiest disease to treat with gene therapy and show the principle of what can be done in terms of getting approval, in terms of understanding the concept of actually having a prescription of what is essentially another biological organism – a virus. Now that’s a completely new concept to the authorities that regulate prescription medicines. But if we have a very good candidate disease, which we do in Choroideraemia, we have very efficient gene therapy, we think we can break down many of the hurdles that we need to to get to that point. Once we’ve got one gene therapy treatment approved and everybody understands what that means and how that should be prepared and how it should be supplied, then we’ll be in a much easier position to bring the other diseases through into the same time point.