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IN TOUCH – Gene Therapy

TX:Ìý 04.06.2024Ìý 2040-2100

PRESENTER:Ìý ÌýÌýÌýÌýÌýÌýÌýÌý PETER WHITE

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PRODUCER:ÌýÌýÌýÌýÌýÌýÌýÌýÌýÌýÌý FERN LULHAM

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White

Hello.Ìý Developing new treatments for eye disease is almost always a series of very small steps, which is why we try, on In Touch, to be very careful how we report on progress so as not to raise false hopes.Ìý Congenital eye conditions have always been particularly resistant to improvements in sight and while not now new gene therapy is an evolving procedure for a range of eye conditions.Ìý Well now the results of a trial in the United States for a group of patients with the inherited condition Leber’s congenital amaurosis, just published in the prestigious New England Medical Journal, is creating considerable, if cautious, optimism.

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Dr Eric Pierce is principal investigator for the trial based at Harvard Medical School.Ìý Mark Pennesi is lead scientist for the trial, he’s based at Oregon Health and Science University.Ìý Well, the work has been done using a new gene editing tool and I began by asking Dr Pierce to just explain what is new about this method of delivery medicine directly into the eye.

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Pierce

So, what’s new about this gene editing approach is instead of adding back a correct copy of a misspelled gene to the retina, gene editing is now fixing misspellings which inactive genes inside the patient’s own retina and the ability to do that is new and we think has the potential to be broadly applicable to treating inherited retinal disorders and hopefully many other inherited diseases as well.

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White

So, when you use the term editing, it is really like editing in the way that we perhaps recognise it editing sound radio or film, it is actually separating and fixing things back together?

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Pierce

Yes, that’s correct, just like you would editing a Word document, the editing approach here is to remove that misspelling, literally cut it out, which allows the gene function to resume.

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White

Perhaps I can bring in Dr Pennesi at this point.Ìý So, tell us more about the trial and what it’s achieved.

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Pennesi

We start first with a very low concentration of the vector and then we increase and treat more and more patients as time goes on.Ìý And so, in this trial, we treated 14 patients and many of them showed improvement in their vision, which was very exciting.Ìý What was exciting too was that when we did a quality-of-life survey many of the patients indicated that they felt that their quality of life had improved following the therapy.Ìý Many of our patients told us stories of what seemingly might be little things to us that they could now do but were actually very big to them – the ability to navigate a little bit better at work and not bump into people or to be able to tell if the light on their coffee maker was on.Ìý And some patients actually went from not being able to read on the eye chart to maybe being able to read the big letter on the eye chart.Ìý We’re not talking about a return to perfect vision but even these improvements were meaningful to the patients.

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White

What kind of patient is likely to benefit from this treatment and is age a likely factor in its success?

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Pierce

I don’t think it’s age specifically that informs us about who could be treated, it’s more the status of their retinas when we’re considering whether they could benefit from this treatment.

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White

And now we know that for very good reasons lots of steps are usually taken between clinical trials and a procedure being widely available, what are the next steps and if all goes well when we might see general availability?

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Pennesi

Well, there’s a defined process for getting drugs approved both in the United States and Europe and the first step of that is a phase one, two trial, which is then.Ìý For rare diseases you often then have to go on and conduct an additional trial with a larger number of patients in usually some form of randomisation where some patients may receive the treatment and some patients may not receive the treatment, so that you can rule out that improvements might be due to placebo effects.Ìý So, we’re hopeful that this will move forward.

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White

It would be fair to say that your chance of getting this kind of treatment would be to be involved in a trial at the moment?

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Pennesi

This is not something that will be on the market immediately, so we would encourage patients to look into trials.

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White

Dr Pierce, to what extent could this work be applied to other genetic conditions which affect the eye?

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Pierce

So, we’re hopeful that CRISPR cas 9 gene editing technologies can be used broadly to treat inherited eye conditions.Ìý We really feel like this is a proof of concept that gene editing can be done safely and effectively in people’s eyes for treating retinal disease.Ìý So, we think this could be applied to other specific types of genetic retinal blindness but also other eye diseases and really you’re demonstrating that gene editing can be done safely in vivo, in people’s bodies.Ìý I hope will help open up the use of gene editing therapies for other inherited diseases as well.

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Pennesi

This is just the beginning for gene editing, this is really the first generation and we’re already exploring even more advanced forms of gene editing.Ìý So, this is something that I expect is here to stay and will really widen our ability to treat a large number of genetic diseases.Ìý So, this is a really important accomplishment for patients.

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White

Dr Eric Pierce, Mark Pennesi, thank you both very much indeed.

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Both

Thank you.

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White

Well, someone who took part in the trial is 22-year-old Olivia Cook, who is joining us from Springfield, Missouri.Ìý Olivia, first of all, can you just explain the kind and degree of vision you had before the trial?

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Cook

Growing up my vision was always fairly bad but I was able to get around.Ìý I had a really limited peripheral field of 18 degrees out of 140.Ìý Doctors kind of compared that to looking through a straw hole, to give it perspective.Ìý And I also wasn’t able to see in the dark like at all and if it was like a dim room, I wouldn’t be able to see very good in there.

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White

I mean how did you get to hear about the trial in the first place?

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Cook

My mum was always really well connected in the vision doctor community.Ìý And when I was about 16, I think, is when the doctor in Texas reached out to my mum and let her know of this opportunity going on in Boston.Ìý So, I definitely did have the doubts about the actual procedure.

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White

What were you worried about?

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Cook

It would make my vision worse.Ìý I only have so much to begin with but I do get around fine, so I was like as long as they don’t make my vision worse I guess that it’s okay but it was a little bit hesitant for me because I had never gotten anything like this before.

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White

And what was the experience like when you did do it?

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Cook

It wasn’t a very long procedure, honestly, I was in the operating room for I think maybe an hour and they put me under, gave me the injection and then when I woke up, they just had a couple of rules that I needed to follow for the next couple of weeks.

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White

What has been the effect on your sight?

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Cook

I’ve mostly noticed a distance in my peripheral and the night vision.Ìý I had no expectation of developing any vision in those areas that I’ve never had vision before and when I finally started to see gunters of light from those sides of my vision, where I’ve never seen anything before, I was pretty shocked about that.Ìý And now I can see better with my left eye in the dark.Ìý I would say like the biggest difference that I’ve recognised was with the night vision I had been at a campfire a couple of weeks ago and usually things get kind of dark and I can’t really see anymore, so I just kind of stay in one place, the other day I was able to walk around and mingle and things, based on just my left eye’s progress.Ìý With my right eye everything was still really dark but with my left eye I was able to actually like manoeuvre like the stumps that we were sitting on and things like that.Ìý And I was like – am I just making that up – like I just wasn’t believing it because it’s still kind of hard for me to believe, even three years post op.

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White

And what’s been the wider effect on your life, if you like, or your attitude?

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Cook

I’m seeing hope of there being progress in the future.Ìý If they were able to inject my eye with this tiny amount of CRISPR and now I’m able to see things in the areas of my eyes that I haven’t ever seen anything before, I can’t imagine where the technology will go in the future.

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White

Olivia Cook, thank you very much for joining us.

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Cook

Thank you.

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White

Well, in case you think that work like this is confined to the United States we should say there is certainly research going on here too, notably at Manchester University.Ìý Well, I’m joined by Rob Lucas, who is Professor of Neuroscience and he studies vision and optogenetics.Ìý So, Rob, I mean first of all, just tell us a bit more about the work on gene therapy which is being done in the UK, which might help with understanding and treatment of genetic eye conditions.

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Lucas

There’s a lot of work going on in the UK on this topic, I think it’s something that really as a community we should be really proud of and it ranges from probably the most widespread activity is people just trying to understand how genes link to disease and then at the other end is people doing clinical trials for therapies which we’ve had stuff going on here at the eye hospital at Manchester.Ìý The work that we do in Manchester really is slightly different to the CRISPR work that you’ve been talking about going on in the States.Ìý One approach to gene therapy is to use it to try and recover or deal with particular individual problems with the genome.Ìý So, if you have mutation of a particular gene, you can target that particular gene for therapy.Ìý The other approach is to think more generally about after you’ve had a progressive degeneration you can maybe try to restore some kind of vision, some kind of photosensitivity.Ìý And one approach to doing that, to which the UK’s been very active, is to look at stem cell therapies.Ìý Ours is a more kind of gene therapy approach to that which is, as you say, this topic of optogenetics.Ìý Often the primary lesion in vision loss is that the photoreceptors, which are responsible for absorbing light, are lost and with optogenetics which we try to do is reintroduce another light sensitive protein to the remaining parts of the retina with the hope, then, that that will recover that fundamental photosensitivity and be useful to restoring some level of vision.

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White

That doesn’t really rely on kind of what we’ve been describing as sort of editing genes, it is introducing something else?

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Lucas

Exactly and so that means that as an approach it has, at least in principle, a wider application because it doesn’t matter what the origin of your photoreceptive loss is, it doesn’t rely on understanding a particular gene or correcting a particular deficit.Ìý The other big advantage of it is that it’s applicable under circumstances in which that vision loss has already occurred and we’re trying to sort of get it back.Ìý There are lots of kind of ideas on the table and things being developed but unfortunately it is a matter of kissing frogs and hoping that some of them turn into princes and of course they won’t all turn into princes.

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White

And, presumably, it’s not just a question of kissing frogs, it’s a question of money as well, isn’t it?Ìý We know that funding for research can be a problem.Ìý Do you receive UK government funding for this kind of research or has it had to rely on funding from charities like Fight for Sight?

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Lucas

We’ve been very lucky and I think it’s generally true for the field that we’ve been able to get money from both of those sources.Ìý So, they do a fantastic job to sort of keep research moving in the right direction and make sure that this type of research is on the agenda in the UK.

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White

Professor Rob Lucas, thank you very much indeed.

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Lucas

My pleasure.

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White

And that’s it for today.Ìý Remember we do really welcome your responses and many of the stories that we cover are the result of the things you tell us.Ìý You can email intouch@bbc.co.uk, leave voice messages on 0161 8361338.Ìý And there’s more information and the chance to download tonight’s and previous editions of the programme from our website bbc.co.uk/intouch.

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From me, Peter White, today’s producer Fern Lulham and studio managers Mike Smith and Jack Morris, goodbye.

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