Episode 4: Gene Therapy Part 2: Applications
Welcome
Hosted by Olivia Moir, Episode 4 explores more about Gene Therapy. You might have already listened to our first episode on this, which featured Professor Simon Waddington who gave us a broad introduction to this field – and if you haven’t, then do check that episode out first as well! This episode we continue that discussion with another wonderful guest, Dr Rajvinder Karda. Dr Karda is both a researcher and professor here at the IfWH, with her role as an Associate Professor of Gene Therapy, as well as leading a team of research focussing on developing pre-clinical gene therapy and RNA editing treatments for childhood epilepsy, including Dravet Syndrome. Today’s episode is going to dive more into her work on this, and the applications of gene therapy in treating non-heritable genetic diseases.
About the Guest
She completed her PhD in Gene Transfer and Neuroscience at Imperial College London in 2016 and currently leads a research team at the IfWH focussing mainly on developing pre-clinical gene therapy and RNA editing treatments for childhood epilepsy, including Dravet Syndrome.
To learn more about her work, visit her page.
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TRANSCRIPT
Speakers:
Host: Olivia Moir
Guest: Dr Rajvinder Karda
00:00:02 Olivia
Hello everyone and welcome back to it all starts here, a podcast focusing on the communication and education of topics in reproductive science and Women's Health.
00:00:12 Olivia
I'm your host, Olivia Moir, and we are back here today to talk more about gene therapy. You might have already listened to our first episode on this, which featured Professor Simon Waddington, and he gave us a broad introduction to this field - and if you haven't, definitely go and check that out first.
00:00:31 Olivia
But today, we're going to be continuing that discussion with the wonderful Dr Rajvinder Karda. Dr Karda is both a researcher and professor here at the Institute for Women's Health. With her role as an associate professor of gene therapy, as well as leading a team of research focusing on developing preclinical gene therapy and RNA editing treatments for childhood epilepsy, including Dravet syndrome. Today's episode is going to dive more into her work on this and the applications of gene therapy in treating non-heritable genetic diseases.
And if you don't know what any of that means, don't worry, because we're going to dive into it today.
00:01:10 Olivia
So, it's such a pleasure to have you on this pod, Dr Karda.
00:01:13 Olivia
Genetics is truly such an interesting field and my favorite. And I can't wait to learn more about your work.
00:01:21 Olivia
So to start us off, please can you tell us a little bit more about where this all?
00:01:26 Raj
Of course, well, thank you first for that lovely introduction Olivia, and as you said, I'm Dr Rajvinder Karda. I'm an associate professor in Gene Therapy at the Institute Women's Health at UCL and to be honest, as a child I always loved science. I think I used to look forward to going to my science lessons in primary and secondary school and that kind of led me into doing a degree in biochemistry at King's College back in 2007.
00:01:48 Raj
And during that time, my passion for research really ignited. And so I continued my academic journey by doing a postgraduate degree in research at UCL as well, which was only at the Institute of Child Health at Great Ormond Street Hospital.
00:02:05 Raj
And this is really the first time I got involved into research, I was with patients, and I started to understand that some medicines like drug treatments are often inadequate and quite limited to some of the patients who have these very severe genetic disorders.
00:02:19 Raj
And so I started to get really intrigued and started research a bit more into gene therapy.
And so this led me to start in my PhD in Imperial College back in 2012 now, and my PhD really involved looking into using gene therapies at tool and looking for inflammation markers in a model for cerebral palsy and during my PhD, I was really interested in trying to develop gene therapy for a very specific neurological disorder.
00:02:48 Raj
And I came across Dravet syndrome from simply just researching and looking into different types of disorders there are out there. And back in 2015, there weren't many genetic therapies or people researching genetic therapies for Dravet syndrome, and because we knew there was a huge unmet need because in Dravet syndrome, current therapies were quite often inadequate and the disease is quite severe, with children with this disease.
00:03:14 Raj
So after a little trial error, I finally came up with some sort of genetic therapy for Dravet syndrome and in 2019 I applied for a grant application - It was successful and that kind of made me start, you know, developing pre-clinical gene therapies and RNA editing treatments for Dravet syndrome and since then, we've been able to use these kind of technologies and RNA editing technologies to develop treatments for other genetic epilepsies in children and other types of neurological diseases too.
00:03:43 Raj
So yeah, that's me in a nutshell essentially.
00:03:46 Olivia
So cool. I think it's. Yeah, I love how that started and it's sort of, It's so applicable I think, to so many people's lives where you kind of like see the more talked about diseases, you know when we're talking about careers in science or like careers in healthcare, you see the things that are often talked about, whether it's like in the media, or you've just heard about it one way or another, but then, these more kind of rare diseases that you know aren't just not talked about as much, or aren't researched as much and the importance of kind of looking into that. So that's really cool.
00:04:21 Olivia
So then sort of to back up a little bit for people that might not know as much about gene therapy, maybe we can get into that first and cover the basics. So further to that first episode that we did with Professor Waddington, let's talk about the different types of gene.
00:04:40 Olivia
So I guess there's viral and RNA editing and maybe you can touch on that a little bit.
00:04:46 Raj
So in order to explain gene therapy, we need to go back to kind of the central dogma of biology and what I mean by that is that you have a DNA which is essentially a genetic code, and that kind of forms RNA and then that forms your protein and everything's all fine and dandy. But if you've got a genetic mutation, so mutation in your DNA code, you have abnormal RNA and then you have abnormal protein in. This leads to genetic disease.
00:05:13 Raj
So essentially what gene therapy does, it comes along and it removes that faulty gene or replaces it with a correct sequence in an individual cells of that specific disorder.
00:05:23 Raj
And generally gene therapy does use harmless viruses to restore the function of that DNA.
00:05:31 Raj
And essentially what RNA editing does, if you go back to the central dogma biology, it interferes with the middle bit which is RNA and therefore interfering with protein. So, it's not directly impacting the DNA at all. So it's kind of fine tuning the therapy to only work on a small part of the RNA and therefore affect the protein production.
00:05:50 Raj
And in my team, we've developed this RNA editing treatment and essentially we also use it in harmless virus to essentially edit the RNA in individual cells and have a long lasting effect because if we use viruses, it’s a one off treatment and therefore in theory it should have a long lasting effect as opposed to if we were using a non viral therapy to do that.
00:06:11 Olivia
Right. Yeah. I mean it's all complex, but I think when you break it down, it's it becomes more clear. But then sort of like leading on from that of gene therapy. Why? I mean, you insinuated towards it, but, why is gene therapy important, like relative to other therapies that can be applied for different diseases? In something that's like related to your genes, let's say. What is the benefit of going directly to that source?
00:06:39 Raj
I mean, that's a very good question, I think the reason why gene therapies are really important is because a lot of these genetic diseasessome of them are rare, some of them not so much.
00:06:49 Raj
They have very limited or no treatment options and if you do have treatment options, they're often inadequate.
00:06:55 Raj
And a lot of these diseases cause very severe symptoms and sometimes people have life long disabilities and they do unfortunately die at a very young age.
00:07:03 Raj
And gene therapy offers a potential treatment to try and cure or actually reduce the symptoms that these patients have because there's literally nothing else out there and so.
00:07:13 Raj
It's another way of trying to treat these patients because unfortunately it's just it's really hard to.
00:07:17 Olivia
Yeah.
00:07:19 Olivia
Yeah, it's sort of like, would you say that it falls into the field of preventative medicine or not necessarily, because it's sort of like the, like, the diseased genes are already there.
00:07:32
Mm.
00:07:32 Olivia
So Gene, you know, therapy is going in to edit it.
00:07:36 Olivia
Is.
00:07:36 Olivia
It's almost preventative, I guess.
00:07:39 Raj
It can be, yeah, you.
00:07:40 Raj
You can edit the gene or you can kind of replace it with the correct sequence as well.
00:07:45 Raj
You.
00:07:45 Olivia
Right.
00:07:45 Raj
You could call call call it that.
00:07:47
OK.
00:07:48 Olivia
OK.
00:07:48 Olivia
Yeah.
00:07:49 Olivia
And then I guess in terms of like applications of gene therapy, so generally like you're looking at this specific 2 rare diseases. Where else could this be applied, for example?
00:08:00 Raj
I mean you can use it for non rare diseases.
00:08:04 Raj
Coming cancer is not is not rare.
00:08:06 Raj
Cancer is quite common, I think. I believe it's one in three or one in four people are likely to get cancer and there are gene therapies developed for this.
00:08:14 Raj
So it it can be applicable for not just rare diseases.
00:08:18 Raj
It really depends on where the need is, because a lot of these diseases.
00:08:20 Olivia
Right.
00:08:23 Raj
Have very limited treatments and that's a problem. You know, current drug therapies are not effective and therefore we need to use the technology that we have and really try to find a therapy that be quite effective. And I think the beauty about gene therapy is that.
00:08:35
Mm.
00:08:39 Raj
If you're using a viral gene therapy is A1 shot treatment because in theory if you give it once it should be there long lasting and you know we could touch upon the different examples later in this podcast. But that's essentially what gene therapy does.
00:08:43
Mm.
00:08:52 Raj
And so it it can.
00:08:54 Raj
It's tailored to that specific disease, which is key.
00:08:57 Raj
Because if you look at drug therapies, you get drug treatment.
00:09:00 Raj
And therapy drug therapy tends to suppress the symptoms or alleviate.
00:09:05 Raj
It doesn't actually go to the root cause of the disease, whereas gene therapy will go to the root cause of the disease and try to rectify that mutation and therefore in theory, that should be a long lasting effect than just getting a cocktail of drugs.
00:09:17 Olivia
Yeah.
00:09:18 Olivia
And would it be applicable to the individual? So like based on their genetic sequence or when you say gene therapy?
00:09:26 Olivia
It's more of like a broad treatment that targets your genes, but it's not specific to the individual.
00:09:33 Raj
Yeah, that's a good.
00:09:34 Raj
So it really depends on the patient population, so.
00:09:39 Raj
If a patient, if patients have all the same mutation, then we can use a very similar gene therapy applied to everyone.
00:09:46 Raj
But if you have a disease where patients all have very different mutations but do have a very similar outcome, similar symptoms outcome. In theory you could use the same gene therapy, right?
00:09:54
Mm.
00:09:58 Raj
But another scenario, if you have patients who have different mutations but have the different have the same disease.
00:10:05 Raj
Yeah, but have different symptoms. Then we got to tailor tailor the gene therapy for those individual patients and therefore it becomes a more of a, a different type of therapy.
00:10:14 Raj
Do and in in that kind of instance you probably would go to use gene editing for example, or even RNA editing to do that, because you have to make a more personalized medicine for that, right?
00:10:24 Raj
It really depends on the disease.
00:10:27 Raj
The patients with specific mutations and the types of symptoms they have and as gene therapists, we really look into the Natural History study of diseases to understand exactly how many patients have this mutation and how many patients present this type of.
00:10:42 Raj
Symptom and how that we can put that into our gene therapy and trying to find a treatment for it.
00:10:47 Olivia
That makes.
00:10:48 Olivia
So it's like tailoring the.
00:10:50 Olivia
Not just the actual therapy, but like the method of how that's going to be applied.
00:10:55 Olivia
Viral versus like RNA editing?
00:10:57 Raj
Yes.
00:10:57 Olivia
Based on the disease.
00:10:59 Raj
Exactly. Exactly because a lot of diseases have a spectrum.
00:11:02 Raj
And what I mean by spectrum is that they can have a different mutation or even have the same mutation represent a complete different symptom.
00:11:07 Olivia
Right.
00:11:10 Olivia
Right.
00:11:10 Raj
So it becomes difficult then, because you're like actually we can't use the same gene therapy for patient A with this disease.
00:11:17 Raj
With patient B, because they're presenting different symptoms and at that point you need to be like, right?
00:11:21 Raj
Need to.
00:11:22 Raj
We need to make this personalized.
00:11:24 Raj
We actually use a different technology to do that.
00:11:27 Olivia
Amazing. And then in terms of like broadly speaking the benefits of viral versus RNA editing, what would you say like if you were going to maybe give three key?
00:11:38 Olivia
Of each.
00:11:39 Olivia
1 You would use them for example.
00:11:41 Raj
So viral therapies are long lasting and you know the the most famous case of the viral therapies has been used is for spider muscular atrophy and spinal muscular atrophy is a very severe chartered neuromuscular disorder.
00:11:44 Olivia
OK.
00:11:52 Olivia
Right.
00:11:57 Raj
Where patients present very severe symptoms.
00:12:00 Raj
Such as unable to walk, unable to talk, they unable to feed or breathe on their own.
00:12:06 Raj
They do die, unfortunately, by the age of 18.
00:12:08 Raj
This is a very small lifespan. These patients have, and so a a a gene therapy using a virus was developed.
00:12:16 Raj
And this is simply by giving a single.
00:12:19 Raj
Administration to patients.
00:12:20 Raj
And after giving a single treatment, all these patients were able to walk, talk, eat by themselves and all live past 18.
00:12:28 Raj
And they're still doing follow on studies with these patients. And in fact this treatment was approved by the NHS in 2021.
00:12:35 Raj
This is readily available for children who were born with spinal muscular atrophy so.
00:12:39 Raj
A very good example of viral therapy was used for very severe neuromuscular disorder. Now only editing this two things you can do with that.
00:12:47 Raj
In my team we use RNA editing in a virus, so very similar to you would give one treatment or be long lasting.
00:12:53 Raj
But you can do these editing as non viral and so these will be repeated administrations.
00:12:59 Raj
They could be for they could also be for neurological diseases too.
00:13:03 Raj
It will.
00:13:03 Raj
You'd need to give it a few more times.
00:13:05 Raj
Won't just be a one off.
00:13:07 Raj
So those are the scenarios where you would use the different treatments depending on if you want it long lasting.
00:13:12 Olivia
Right.
00:13:12 Raj
Or if you wanted to repeat it to treat a disease over a period of time.
00:13:18 Olivia
OK. Umm.
00:13:19 Olivia
That makes sense. Thank.
00:13:21 Olivia
And then in terms of like the actual timing of applying these gene therapies, so in Java syndrome, this is already developed.
00:13:31 Olivia
It's like in early childhood. I guess the application would be of the gene therapy.
00:13:36 Raj
For giraffe syndrome, yeah, it it depends which giraffe.
00:13:36 Olivia
I.
00:13:39 Raj
The patients do present the disease around six months to a year of age and it really depends when they get diagnosed. So ideally you want to give the gene therapy as soon as possible.
00:13:49 Olivia
Right.
00:13:50 Raj
But they are, so they are.
00:13:52 Raj
There is a 2 clinical trials in fact for girvave syndr.
00:13:57 Raj
Um 1 is a non viral 1 is a viral therapy and this goes back to what we.
00:14:00 Olivia
OK.
00:14:02 Raj
So the viral therapy is using a a a harmless virus to deliver a sequence of DNA to rectify the genetic mutation in patients.
00:14:12 Raj
So they are delivering this gene therapy very early in development. So from the.
00:14:17 Raj
Of one to two eight years of age.
00:14:20 Raj
There's a multi center clinical.
00:14:22 Raj
So this is happening in the US, UK and Australia, whereas a non viral gene therapy has a larger age group.
00:14:25 Olivia
OK.
00:14:28 Raj
You're admitting the treatment to ages between 2 and 18 years of age.
00:14:33 Raj
But you're doing 3 treatments over a period of 6 to 9 months, and you're looking at the the.
00:14:36
OK.
00:14:38 Raj
Following the patients, seeing how it's working and the reason why that's happened is because.
00:14:40 Olivia
OK.
00:14:43 Raj
These types of non viral therapies have been used for Huntington's disease because those patients present it later in life and.
00:14:50 Raj
These number of therapies have worked in different types of diseases too, so the viral therapy has gone early in development because the spinal muscular clinical trial which I just discussed, they administer the the gene therapy very early in development. The first you know the youngest patient that rece.
00:15:10 Raj
Gene therapy, I believe.
00:15:12 Raj
Days of age I think the median age was 21 in the last clinical trial.
00:15:16 Raj
So what they've learnt is that the earlier you go with viral therapies, the better the.
00:15:21 Olivia
Right.
00:15:21 Raj
So that's why the age group for the viral therapies is smaller than for the non viral, which is 2 to 18 months of 18 years of age.
00:15:31 Raj
So you don't know, we're still looking at the outcome because it just started.
00:15:35 Raj
But we do know from the non viral therapy Drava syndrome, they've been able to reduce the seizures outcome in these patients.
00:15:42 Raj
That's a very good outcome for the Travis Indian community because it's working really well.
00:15:46
Yeah.
00:15:46 Raj
So you can see that there's different ages that they're administering it to and it's all about understanding how these mechanisms work.
00:15:53 Olivia
Definitely.
00:15:54 Olivia
And I guess like the other important factor that just came to mind as well is like in terms of the timing?
00:16:00 Olivia
So we said we're gonna talk a little bit more about it.
00:16:03 Olivia
We can do that now is.
00:16:06 Olivia
Diseases that are heritable versus non heritable.
00:16:09 Olivia
So Drove Syndrome is an example of non heritable, and so maybe like a background on what that means really, that's.
00:16:16 Raj
Absolutely.
00:16:17 Raj
So heritable diseases happen when there's a mutation in your germ cells, and germ cells are your reproductive.
00:16:23 Raj
So that means that this mutation will be permanent in Charles DNA and therefore will be passed on to the next generation.
00:16:31 Raj
Non heritable mutations happen in somatic cells and essentially these cells are non reproductive cells.
00:16:37 Raj
And these mutations happen by environmental factors or happen if there's some sort of issue with DNA replication that's occurred during development. But these mutations are not passed on to to the next generation.
00:16:49 Raj
That's the difference and with with Dravet syndrome, you know 90% of the patients have sporadic mutations that cause.
00:16:57 Raj
Their their disease itself.
00:16:58 Olivia
Yeah.
00:16:58 Raj
And that's what the difference is between the two.
00:17:00 Olivia
Yeah, that makes sense.
00:17:04 Olivia
You would see the disease presenting. I guess that's part of, you know, what leads to it presenting between 6 and 12 months of age.
00:17:11 Olivia
Said yeah.
00:17:12 Olivia
And then in terms of like, so two questions off that.
00:17:16 Olivia
So in terms of like.
00:17:18 Olivia
The gene therapy that you are administering to.
00:17:22 Olivia
A child, let's say.
00:17:24 Olivia
Is it different depending on if it's a somatic cell? So like if it's a non heritable disease versus a heritable disease, would the gene therapy be effective if it's heritable, like can you do that to reproductive cells for example?
00:17:40 Raj
So that's a good question, I think.
00:17:44 Raj
It's two questions you've asked there in terms of.
00:17:48 Raj
Talking about heritable diseases and using gene therapy and whether that affects the reproductive cells, right.
00:17:53 Olivia
Yeah, yeah.
00:17:53 Raj
It's two different.
00:17:54 Raj
So the first thing is the heritable gene.
00:17:58 Raj
Sorry, gene therapy, heritable diseases is the very good example of spinal muscular atrophy, right?
00:18:03 Raj
So as I mentioned.
00:18:05 Raj
And I think we talk about it quite a lot because it's such an amazing study that's happened and it's something that's unheard of with these children.
00:18:12 Raj
Is that spinal muscular atrophy is very severe that soon as a child is born, it will start to present the disease.
00:18:18 Olivia
Right.
00:18:18 Raj
And so.
00:18:20 Raj
They use a gene therapy for spinal muscularity, as I mentioned, which is a virus form, and gave a single administration to patients very early in development and they all were able to walk and talk on their own. And we live past 18 months, which is amazing because that.
00:18:35 Raj
Happened before.
00:18:37 Raj
So that's a good example where you can use gene therapy for heritable disease. Now using gene therapy to target reproductive cells is a very different subject, because that can be unethical because you can't really mess around with those.
00:18:48 Raj
Things and you know the studies that have ongoing where in pre clinical using animals to look into if you are trying to treat a disease are you targeting reproductive organs?
00:18:58 Raj
Because that's something we don't want to do, you know, and those things we do look into as researchers is we look into the reproductive organs and see are we?
00:19:00 Olivia
Yeah.
00:19:08 Raj
Are we infecting this with our gene?
00:19:10 Raj
Because actually we don't want to do that. What we want to do is actually treat the disease itself.
00:19:15 Raj
These are things that we do look into.
00:19:17 Raj
So yeah, so we don't use gene therapy to treat reproductive cells.
00:19:21 Olivia
Yeah.
00:19:21 Raj
What we do is treat the the disease that has happened because there is a.
00:19:27 Raj
I can't say the word.
00:19:28
Now.
00:19:30 Raj
It is.
00:19:31 Raj
It's a heritable mutation that's happened, and therefore it's caused this different type of severe disease and that's what we're trying.
00:19:37 Raj
Treat.
00:19:37 Olivia
Yeah, that makes so much.
00:19:39 Olivia
And then like in terms of, so targeting your therapy towards non reproductive cells, is there a way that you can do that?
00:19:49 Raj
Yes, I mean, I mean that's.
00:19:50 Raj
Of what we.
00:19:50 Raj
With all of all of the gene therapies.
00:19:54 Raj
So you know with, with spinal muscular, I keep going back to this is because it's a very good example to you.
00:20:00 Raj
It is mainly caused by motor neurons, so it's neuron cells that are.
00:20:05 Olivia
Yeah.
00:20:05 Raj
It just so happens that this mutation has been passed on from 2. Parents have a recessive gene for this particular.
00:20:13 Raj
SM1, gene, and therefore the babies born with spinal muscular atrophy.
00:20:17 Raj
And it's.
00:20:18 Raj
The most neurons that are affected by.
00:20:20 Raj
So those are not, they're not reproductive cells, they're actually neurons that are being targeted. And so therefore you are using gene therapy to fix a mutation that.
00:20:29 Raj
That is not in a reproductive cell, and in this case it's a motor neuron cell.
00:20:34 Olivia
Right. OK.
00:20:36 Olivia
Wow, I feel like I've learned so much.
00:20:38 Olivia
I guess, circling back to Dravet syndrome and your applications of gene therapy, we haven't necessarily established what currently is happening in the field of that and in your research work in particular, where are we at right now?
00:21:09 Raj
Currently there are many different groups around the world that are developed different types of gene therapies for Girvase syndrome.
00:21:16 Raj
And two of the pre clinical projects are happening in my team. So we've developed a a viral mediated gene therapies for both them are one is targeting a DNA one is targeting RNA and so at the moment we have.
00:21:24 Olivia
Yeah.
00:21:28 Olivia
OK.
00:21:30 Raj
Developing the treatment so that we can get all the experiments, all the right experiments done to make sure our both our treatments are effective before we take it on to a clinical trial.
00:21:39 Raj
So we're about four years away from getting to that point, but I'm hopeful that we can get this done because you know, there are many patients who are affected by this very severe disease.
00:21:49 Raj
Now, as I mentioned, there are two different types of therapies available in the clinical trial at the moment. So one of them is a non viral therapy.
00:21:56 Raj
That's the one that's been administered to patients between the age of 2 to 18 months, and they've shown some very good outcomes with it, able to reduce the very severe seizures that are happening in patients.
00:22:05 Raj
And they're just about to start their gene therapy clinical trial for Java syndrome, which is again is recruiting patients from the age of 1 to 8 years of age in the US, UK and Australia.
00:22:18 Raj
So like I said, this is a very exciting time for patients with Java syndrome and the driver syndrome community because.
00:22:24 Raj
You know, we know that.
00:22:25 Raj
It is a very severe childhood genetic disorder and we know that current therapies are.
00:22:30 Raj
Often inadequate, and you know they can.
00:22:34 Raj
Anesthesia medications can suppress the seizure frequency, but the seizures are still there.
00:22:40 Raj
You still have this.
00:22:42 Raj
Developmental delay and cognitive delay that does occur with these with this disease as well, so.
00:22:48 Raj
I'm very glad that there's different people working on.
00:22:50 Raj
I'm glad that we're working on it and we're trying to work towards trying to get these two patients as soon as possible.
00:22:54 Olivia
Yeah, definitely.
00:22:56 Olivia
And then I guess the other question that I would have like in this field of Drava syndrome, is there something that you find or even just gene therapy in general?
00:23:05 Olivia
There something that you find is a common misconception.
00:23:08 Olivia
Know whether it's with.
00:23:09 Olivia
Colleagues, or it's with, you know, your friends or family who maybe don't have a background. Like, do you find that there's anything that people will commonly just sort of assume? But you know, isn't true necessarily?
00:23:22 Raj
I I definitely it's a very good question because.
00:23:25 Raj
One of the things that they probably would be have misconceptions about is because when you talk about gene therapy, you discuss viruses as soon as you hear a virus because of the COVID pandemic, everyone's like, what is that?
00:23:38 Raj
It's almost a really bad thing.
00:23:39 Olivia
Yeah.
00:23:40 Raj
But if you don't know about gene therapy, you start to you. You would assume the worst of it because it's a virus.
00:23:46 Raj
But actually in fact, it's about educating everyone around you and educating the lay audience and also.
00:23:51 Raj
You know, a lot of parents who may not know about what gene therapy is and also just letting them know that it's it's it's quite safe because there's many different clinical trials going on for gene therapy at the moment and non viral gene therapy. You know both virus.
00:23:55 Olivia
Yeah.
00:24:04 Raj
Non viral. So there is a lot of data coming out showing that how safe it is and how it is.
00:24:10 Raj
Very effective in trying to treating very severe and.
00:24:12 Raj
You know all the way to treating cancer and different types of therapies too.
00:24:17 Raj
It's all about.
00:24:19 Raj
Feeding that information to the lay audience and letting them know that actually gene therapy is OK and it can be applied to many different disorders and help them in the long run.
00:24:24 Olivia
Yeah.
00:24:28 Olivia
Yeah. And I guess also like really kind of.
00:24:32 Olivia
Clarifying that point as well of like this is being applied to your somatic cells versus reproductive cells.
00:24:39 Olivia
And you know, I just, I feel like there's.
00:24:41 Olivia
Importance in like identifying and separating those two things.
00:24:45 Raj
Definitely.
00:24:47 Raj
And it's, yeah, it's about having these kind of.
00:24:49 Raj
We're really informed that to the wider audience because, you know, it's really important to do that as gene.
00:24:51 Olivia
Yeah.
00:24:56 Raj
We do get involved with a lot of patient groups because that helps us to feed an information to our research.
00:24:59
Yeah.
00:25:03 Olivia
Yeah.
00:25:03 Raj
Because we need to understand is OK.
00:25:06 Raj
How is this affecting the individual?
00:25:08 Raj
How is this affecting their?
00:25:09 Raj
Do we need to inform their parents too?
00:25:11 Raj
Going.
00:25:12 Raj
So it's it's a huge, it's a lot of people involved in into developing a gene therapy.
00:25:18 Raj
Not just what your research is is a bigger picture.
00:25:21 Olivia
Yeah.
00:25:21 Raj
We need to make sure this is everyone.
00:25:23 Raj
It works and everyone understands what's going on as well.
00:25:26 Olivia
Definitely. It's so important. And then also I.
00:25:31 Olivia
I have a question for you about, you know your specific field of study like like you said at the beginning.
00:25:36 Olivia
When you were kind of getting into this and you kind of, you saw the importance of looking into rare.
00:25:38
Mm.
00:25:44 Raj
Yeah, yeah.
00:25:45 Olivia
Diseases that maybe aren't as studied was that hard, like getting into a field that you know isn't as maybe funded or field that isn't as focused on or there isn't as many years of research, I mean.
00:25:59 Olivia
I'm sure that it presented unique.
00:26:02 Olivia
And do you have advice for anyone who you know, maybe is thinking about getting into that?
00:26:08 Olivia
Field or or just interested in you know.
00:26:13 Olivia
Maybe doing something that isn't done often?
00:26:16 Raj
Yeah. No, definitely.
00:26:18 Raj
I would encourage everyone to do it because you know at that time I was quite junior in trying to understanding what gene therapy.
00:26:24 Raj
I hadn't finished my PhD at that point and I didn't really know much about genetic epilepsies because my my my PhD had nothing to do with.
00:26:33 Olivia
Yeah.
00:26:33 Raj
And so really what I started to do was Googling.
00:26:37 Raj
I used Google quite a lot and Googled, you know, epilepsy experts at UCL.
00:26:42 Olivia
Yeah.
00:26:43 Raj
And I.
00:26:43 Raj
A lot of door knocking.
00:26:44 Raj
I went around, UCL said.
00:26:46 Raj
Hello I'm Raj.
00:26:47 Raj
Can you help me with this? And it was literally that.
00:26:50 Raj
Was me going around?
00:26:52 Raj
Just talking to people and people who.
00:26:53 Raj
Is this person that keeps coming around?
00:26:54
I keep.
00:26:56 Raj
But I was quite like determined that I wanted to learn.
00:26:59 Raj
I wanted to understand this and that didn't put me off in terms of there wasn't any research done, but I was like, well, if there isn't someones gotta do it, we've gotta figure it out. We have to figure.
00:27:00 Olivia
Stephen.
00:27:08 Raj
Out and it came to really establishing collaborations around everywhere because that's really key is like feed information to what I need to learn. And therefore I can understand how we're going to do this.
00:27:14
Mm.
00:27:20 Raj
And so that took many years to do that.
00:27:22 Raj
Really knocking on doors trying to get.
00:27:25 Raj
You know doctors who work with patients directly at great Arm St. Hospital to work with you.
00:27:28 Raj
That really fed into the whole research.
00:27:31 Raj
So it took a bit of time, but I will tell people to not give up.
00:27:33 Raj
Just literally requires.
00:27:35 Raj
There's a lot of going out there, networking, speaking to a lot of people, speaking to some experts in the field, getting as much information as you possibly can do to really formulate your ideas.
00:27:46 Raj
Honestly, it will be.
00:27:47 Raj
You know, I've I've done it. And many other people have done it too, but honestly requires patience and a lot of a lot of networking.
00:27:54 Olivia
So good to hear.
00:27:56 Olivia
OK. And then I guess to wrap things up.
00:27:58 Olivia
I mean in the field of Drava syndrome in particular, what are you hopeful?
00:28:04 Olivia
Like what are you hoping to see? You sort of mentioned like, you know, in the next 4 years, you're hoping to get it clinical?
00:28:11 Raj
Yeah.
00:28:11 Olivia
Your therapies, I guess that would be.
00:28:14 Olivia
What you're looking?
00:28:15 Olivia
But you know, even beyond that, what is the future of Java syndrome and epilepsy?
00:28:21 Olivia
Epilepsy and gene therapies look like for you.
00:28:24 Raj
Yeah. I mean, as I mentioned with Dravet syndrome, I'm I'm terribly excited about how the Phillips moving you know because.
00:28:32 Raj
There's two treatments available in clinical trial, you know for Travis injure and the nonviolent viral.
00:28:37 Raj
And we're developing some treatments too, and hopefully we should get that into into clinic in the next couple of years and as many teams across the world are working on different types of therapies for GAVI syndrome.
00:28:46 Raj
So it's a very.
00:28:47 Raj
It's an amazing time to work in gene therapy, but also you're seeing these really great outcomes from these clinical trials.
00:28:54 Raj
Really beneficial for the patient 'cause. That's the main thing is we're doing.
00:28:58 Raj
Benefit the patients with driver E syndrome because you know there's there's no other treatment that's working effectively.
00:29:04 Raj
Hmm. You know, current drug treatments aren't working really well.
00:29:09 Raj
In terms of the field, its work is moving in the right direction I believe, and I think as time moves on and as time.
00:29:17 Raj
Starts to develop.
00:29:20 Raj
We're starting to see that we can apply these gene therapies for many different.
00:29:23 Raj
So I think the field of gene therapy is going to move in, is going to vastly improve because so much is changing. As I mentioned, there's just, you know, your traditional gene therapy where you use viruses to replace a defective gene or using non viral therapy to.
00:29:37 Raj
Manipulate DNA. But you've also got, you know, new technology like gene editing or editing, where you can make much more precision medicine and try to treat different diseases.
00:29:47 Raj
So I think it's just gonna. It's gonna continue to grow and I and I honestly believe in my lifetime, at least I think you'll be able to buy gene therapy over the counter for something for sure. I think you will be able to.
00:30:00 Raj
I mean, we've already seen it with Covic.
00:30:02 Raj
Yeah, that was an M RNA therapy and also the AstraZeneca Advair. That was a gene therapy.
00:30:08 Raj
You know, I think people forget that some people in the population UK are very have received some form of gene therapy without realising they've.
00:30:15 Raj
It.
00:30:15 Raj
Yeah. So definitely, I think the field of gene therapy is going to vastly improve and change over the next couple of years.
00:30:22 Olivia
So cool. You heard it here first, guys.
00:30:25 Olivia
Thank you so much for coming.
00:30:26
You're welcome.
00:30:27 Olivia
It's been so great to learn from you.
00:30:28 Raj
You're welcome. Thank you for having me, it's been a really great chat.