Using Viral Vectors To Stop Epilepsies - José M Serratosa, Hospital Universitario Fundación Jiménez Díaz, Spain
People with an epilepsy might be nervous about getting "gene therapy" - but in today's mini-episode, in part 2 of 2, epileptologist José M Serratosa is asked if he would get gene therapy and why(!), explains the use of viral vectors for treating genetic epilepsies, where we are in preclinical development, what is next, and what is also holding us back!
Reported by Torie Robinson | Edited and produced by Carrot Cruncher Media.
Podcast
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00:00 Torie Robinson
Why would you give it a shot?00:02 José Serratosa
Well, I think, first, I don't want anybody to take out a piece of my brain!00:07 Torie Robinson
Fellow homo sapiens! Welcome back to, or welcome back to: Epilepsy Sparks Insights.
Lots of people with an epilepsy might be nervous about getting "gene therapy" - but in today's episode, I ask our fabulous guest in part 2 of 2, epileptologist José Serratosa, if he would get gene therapy! Jose tells us about the use of viral vectors for treating genetic epilepsies, where we are in pre-clinical development, what is next, and what is also holding us back (if you have listened to our other episodes, you can probably guess what this is!)!
Please don’t forget to like, comment and subscribe to the channel - if you haven’t already - so that we can educate regarding the epilepsies to more people around the world.00:50 José M Serratosa
I am a neurologist and epileptologist with a special interest in genetics, but, the problem with viral vectors is the cost of the production. Also, because we need a large quantity of vector and we need a good quality with many quality controls. So, the production of viral vectors is quite expensive and of course, the clinical trials are always expensive. To finish the point: if there is only one injection in a lifetime, you can prevent immune reactions, hopefully. If you inject several times, that could be a, you know, a bigger problem, because then there could be a reaction to the second, third…01:48 Torie Robinson
So, where are we in terms of the stage of the research into the use of viral vectors? We spoke about using rodents. What's the next stage and when may it reach humans?01:59 José M Serratosa
Well, the next stage (after showing that something works in animal models) is looking at the toxicology, finding the right dose, looking at the distribution… it's not very exciting, but it's something that has to be done. And, after that, you may be allowed - if everything works out well to do clinical trials. So, I think we are in between the last stages of preclinical development, in some cases doing the toxicology, distribution, etc. tests, and clinical trials. So, I think in the next year we'll see some clinical trials.02:47 Torie Robinson
Wow. If I was pre-resection, I would put myself forward. I'd just be like “Mate, go for it.”.02:53 José M Serratosa
I would.02:54 Torie Robinson
You would as well, would you!02:55 José Seratosa
Yeah.02:56 Torie Robinson
That's important to hear actually, really powerful. You, the clinician, the scientist, you would give it a shot. Why would you give it a shot?03:05 José M Serratosa
Well, I think first: I don't want anybody to take out a piece of my brain. I think neurosurgery is, you know, it's of course an aggressive procedure.03:17 Torie Robinson
Especially resection.03:19 José M Serratosa
With the exception of, you know, the minimal invasive procedures03:23 Torie Robinson
Laser ablation and…03:25 José M Serratosa
Yeah. For many resections you need to open the skull with a big, quite large opening. So that makes one point and also, I think you may go to the problem that every, or each specific patient has. So, you can maybe look at the deficit that is present in a patient. For example, if you need more potassium channel activity, go with potassium channels. If you need a receptor activity, etc. So, you can probably look. And also, because it would be an outpatient procedure with just one simple injection.04:19 Torie Robinson
You're saying that each individual vector implantation/injection would be tailored to each individual person? It's not, like, “one size fits all”, like, you know, here's a jab/a vaccine for something. It would be tailored for each individual person?04:34 José M Serratosa
We don't really know…04:36 Torie Robinson
Okay.04:37 José M Serratosa
…but it may be, in the future, that for each (for example - I am just guessing)... for a focal cortical dysplasia, you need this type of gene and channel. And for maybe a tumour (a benign tumour), you need another type of channel. Maybe.04:59 Torie Robinson
Not knowing is annoying, but also, it's quite exciting and inspiring, I think, for research. It's like, God, we need to do this. We need the money from funding bodies to be able to literally do it….!05:12 José M Serratosa
Right.05:12 Torie Robinson
You were making me think of this... so, it was this Australian study about… they calculated the cost to society, on average, of a person with an epilepsy over a lifetime. I can't remember the amount, but it was something crazy, like, it was high. It was in the millions, I think…05:33 José M Serratosa
Yeah.05:33 Torie Robinson
…for each individual. And then, so, thinking about that, when you said, okay, you could go in, have a jab, leave after half an hour and the problem could be solved… the amount of… just the benefit to wider society of that...would just be wild! Amazingly wild though!05:54 José M Serratosa
Although it may cost, also, 1 or 2 million [EUR/USD/AUD/GBP] because these treatments are... now, at least, now, very expensive.06:03 Torie Robinson
But do you think perhaps the cost could come down? A bit like genome sequencing - [it] used to be extraordinarily expensive; now you can get it done for well, depending… depending where you go, but you can get it done for like 500 euros or something.06:14 José M Serratosa
Yeah. I think it will get less expensive. I think in many years.06:19 Torie Robinson
Fair.06:20 José M Serratosa
We are working in the field of progressive myoclonic epilepsy; Lafora disease. This is a deadly disease for 95% of the patients. And we are trying to replace the abnormal gene in the patients. But now we are almost done with what we call proof of principle, showing that it works in mice. So, it does work in mice. The Lafora bodies (which is an abnormal deposit in the neurons) and other cells in the brain are less than in non-treated animals and the features, the clinical features, are also less in the treated animals. So, we are trying to, you know, go to the next preclinical studies so we can go to clinical trials maybe in a few years. It's a long process and it costs, that's a problem, millions of dollars, euros…07:35 Torie Robinson
Thank you to José for his insight into the research into the use of viral vectors to treat the epilepsies! We shall get there...just never soon enough.
Check out more about José and his work on the website torierobinson.com (where you can also access the podcast, video, and transcription of this episode), and, if you haven’t already, don’t forget to like, comment, and subscribe to the channel, share this episode with your friends/colleagues/family members, whoever it might be (!) and, see you next week! -
José M. Serratosa is a neurologist specialising in epilepsy in Madrid. He obtained his Doctorate in Medicine and Surgery from the Autonomous University of Madrid . After completing his residency at the Neurology Service of the Puerta de Hierro Clinic , he trained in epilepsy at the University of California, Los Angeles (UCLA). Subsequently, he was appointed Associate Researcher in the Department of Neurology at the UCLA School of Medicine.
José has a strong scientific interest in the characterisation of epileptic seizures, surgical treatment of epilepsies , genetics of epilepsies, progressive myoclonic epilepsies (including Lafora disease), neuroimaging studies in epilepsies and mechanisms of resistance to anti-seizure medications and the development of adverse effects to them.
José has published numerous articles in international journals and has contributed chapters to specialised books. He has also served as Associate Editor of the journal Epilepsia , published by the International League Against Epilepsy , and is on the editorial board of the journals Seizure and Epilepsy Research . He is also a member of the Genetics Commission of the International League Against Epilepsy.
In 1995, José joined the Neurology Service of the Jiménez Díaz Foundation , where he established the Epilepsy Unit and continues to carry out his clinical, teaching and research work. Since 1995 he has directed the Epilepsy Genetics Neurology Laboratory.José discovered the locus of the first gene for Lafora Disease and was the co-discoverer of the EPM2A gene; one of the two genes where mutations are found in Lafora Disease.
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X/Twitter: serratosa
LinkedIn: jose-serratosa
Hospital Universitario Fundación Jiménez Díaz: fjd.es
ILAE: national-chapters/spain
ResearchGate: Jose-M-Serratosa