Preventing Seizures Using Stem Cells?! - David Spencer, Oregon Health & Sciences University, USA
Hear about research into a new way of inhibiting temporal lobe seizure activity through GABAergic interneuron cell therapy! With epileptologist and neuroscientist David Spencer.
Reported by Torie Robinson | Edited and produced by Carrot Cruncher Media.
Podcast
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00:00 David Spencer
“At least our first 2 participants that I know their outcomes very well are doing extremely well from this surgery. And our participant has actually been seizure free for almost a year now.”00:10 Torie Robinson
Fellow homo sapiens! Welcome back to Epilepsy Sparks Insights.
Now, today, you’ll hear me get a little excited! So, imagine if stem cells could be developed and used to prevent seizures from occurring….! Well, today, neurologist and neuroscientist David Spencer shares with us his research into inhibiting temporal lobe seizure activity through interneuron cell therapy (which he shall kindly explain - because, yeah, I have no idea how to do that)!
But, please don’t forget to like, comment and subscribe. Your comment and like will help spread awareness and understanding of the epilepsies around the world.00:49 David Spencer
It's great to be here, Torie, and thanks for the invitation. I really appreciate it. So, I'm an adult epileptologist. I work in the United States in Portland, Oregon, at a centre called Oregon Health and Science University. So, we have a comprehensive epilepsy centre, and we take care of lots of people with epilepsy - from mild epilepsy to kind of the most complicated, challenging cases - helping with medical management, in some cases helping with guiding people through the process of epilepsy surgery or more kind of advanced therapies for treatment of epilepsy.01:21 Torie Robinson
Could you tell us how much of your time is spent, say, in clinical work versus research?01:26 David Spencer
I would say I'm more of a clinician than a researcher. I probably spend two thirds of my time doing clinical work. A little bit more administrative role lately, actually, has taken over a little bit(!), but it's interesting as well. And then research maybe, I mean, a third or so.01:43 Torie Robinson
I mean, to me personally, and many people I speak to, research is crucial when it comes to giving hope to people affected by the epilepsies. What do you focus on when it comes to the research?01:53 David Spencer
Yeah, I've been interested in a number of different areas. One is neuroimaging of epilepsy; trying to understand better how we can identify a seizure focus, what kind of different tools can be used to understand the brain structure and function. I've been interested in neurostimulation or neuromodulation - I know you had a podcast on that not too long ago covering that topic. And then I think something we're hopefully we're going to talk about a little bit today - which is a new area for me - is looking at cell therapy for treatment of epilepsy.02:26 Torie Robinson
So, tell us about that cell therapy. I know it sounds a little bit scary to some people, but I think it sounds fascinating. What are the basics of that?02:34 David Spencer
It's a really interesting, I think really appealing concept to me and to patients that I've talked to about it. And the idea is that, I mean, it's a little bit of a simplistic idea maybe, but in the brain when someone's having seizures or is more prone to seizures, there's some imbalance between the kind of the cells in the brain that are more excitatory and cause the cells that they're connected to to fire more rapidly, and then those that are inhibitory or might kind of be the breaks or slow down the firing of brain cells or neurons. And so, you know, trying to keep that balance between excitation and inhibition is really critical to help stabilise things and prevent seizures from happening.
So, the approach with the cell therapy is kind of a line of cells has been developed that are kind of the natural inhibitory cells of the brain. And the strategy then, with this research, is to actually implant these cells into the seizure focus. And they have the ability to make connections with the person's own brain cells in the area and kind of add to the inhibition or the ability to kind of break things or slow down things to prevent seizures.03:51 Torie Robinson
Are these, like, complete cells that you put in or is this like, the whole shebang - you put in, like, “lumps”?03:57 David Spencer
It's the whole shebang! Yeah, so these are cells that have been… they're derived from stem cells, but it's not actually stem cells. They're developed from stem cells and then they develop down a path into these actual inhibitory cells that are mature cells. The challenge of course is getting them into the right spot safely, so, these are actually surgically implanted into the seizure focus and then they can migrate, they can recognise cells in the area, make connections, make synapses, and actually integrate into the circuitry.04:38 Torie Robinson
This is amazing. So, thinking of these stem cells, how do these specific stem cells, maybe if I'm going to, oh, this is an… will have an obvious answer, but how do they know to form brain cells instead of other types of cells if they're stem cells?04:55 David Spencer
That's the… in the actual development of the cell line that's used for the therapy, you can give different sort of trophic factors or different sort of treatments to kind of encourage them down a particular path of development so they can be kind of trained to develop into a certain cell type.05:14 Torie Robinson
It's like focusing on a specific, you know, muscle area and you… and you train that in the gym and you've kind of done something similar for these stem cells to become the neurons that we need?05:24 David Spencer
Exactly, so you can get a very kind of pure culture of these inhibitory cells that... So, the important, one important thing is that they no longer have the capability to divide. So, the stem cells can kind of keep dividing and make more and more cells. These are a little farther down the path, so they're actually now kind of determined to be inhibitory cells. And if they're implanted, then they will no longer divide. So, there's, you know; the idea is to not have the risk of having cells that continue to divide and could potentially develop a tumour or something, so they're carefully screened to avoid that problem.05:58 Torie Robinson
That’s so cool. At what stage in this research are you? So, have you been using rodents, or more mature… or other animals? Have you used them in humans yet?06:10 David Spencer
Yes, all the above. So, there's a long history of what we call preclinical studies - you know, animal studies using animal models of epilepsy -, a lot of them done in rodent models - so, mice that have epilepsy that's resistant to treatment with Anti-Seizure Medications and then have the cells implanted. And, I mean, they did remarkably well. About two thirds of the mice became completely seizure-free - even in these very, kind of, resistant, refractory models of epilepsy! So, that was very, very encouraging. There were a lot of studies to look at, you know, how do you scale this up? What would be the right kind of dose of cells for a human? Because a human's temporal lobe, hippocampus (which is what we're targeting right now), is much larger than a mouse's! So, there was a lot of work to look at that.
About 2 years ago, we started participating in this first “in human” study of inhibitory stem cell implants in people. So, at our centre, we had the second patient in the world who ever received this therapy, which was very exciting! And now, there have been 7 patients who have received this therapy, 3 more planned. So, kind of the first wave of 10 implants is well underway and, and planned.07:35 Torie Robinson
And the outcomes so far - in the humans - have they been, overall positive?07:39 David Spencer
It’s been very positive. You know, we…heavy note of caution because this is very, very early days!07:44 Torie Robinson
Yeah.07:44 David Spencer
This stage of the study is focused mostly on safety. So, we want to make sure that there aren't any unexpected, unintended consequences of doing the implants. We're studying first, people… like a very narrow group of patients that have seizures coming from the temporal lobe and in particular coming from the hippocampus (a lot of your viewers or listeners may be aware of all this, but the middle part of the temporal lobe). And so, one nice feature of that design of that selection of people is that if they don't get an adequate response or there's any complications, they could still go on to have what might be a more traditional kind of treatment for drug resistant epilepsy coming from the temporal lobe, which might be a temporal lobe surgery or laser ablation.08:37 Torie Robinson
What could potentially be the benefits of a person having cell therapy compared to say a resection or laser ablation?08:47 David Spencer
Yeah, that's a great question and that's one of the reasons why I find this area really, really exciting is that it's… the idea is that it's more potentially of a restorative therapy rather than a destructive approach. So, with epilepsy surgery, you know, we're trying to… people who've been through this process know there's a long, often a long process of trying to identify exactly where the seizure focus is, would it be safe to treat surgically, and then, you know, with surgery, with laser ablation, with different techniques, the idea is to try to identify and basically remove or destroy the tissue that's causing the seizures. And, you know, we do go to great lengths to try to ensure the safety of that. But sometimes, there are some trade-offs of some of that tissue may still be functional, even though it's causing problems by initiating the seizures. So, with this approach, the idea would be you could, you know, effectively treat the seizures without having to destroy or remove any brain tissue. You’re kind of rebalancing or restoring function rather than being a destructive procedure. So, that idea is really, really appealing.10:01 Torie Robinson
Gosh, yes, no, totally. I mean, one of the biggest things that, well, I'll moan about as well as other people affected, and who may have had a resection is that - memory, oh my goodness, cognitive function is just horrific, often. Not for everyone, as you know, but sometimes, especially if you've had the resection, it can be, feel like a real, sort of, cognitive disability sometimes! And so, to me personally, that's why your work sounds very appealing. If you can prevent that from happening, that would be pretty fabulous.10:35 David Spencer
Yes, I mean, we can't make claims about that yet(!), but I think that is one of the reasons this approach is being looked at. And that is clearly one of the risks with the surgical sort of approach, with a resective surgery approach.10:51 Torie Robinson
Have you identified any side effects of this treatment so far?10:55 David Spencer
At this stage of the research, the main focus is on safety. And so, we have not seen any serious adverse events, any unexpected side effects from surgery so far. Again, 7 people have received the therapy to this point. The participant at our centre is now about a year and a half into treatment and the longest person is coming up on two years pretty soon this summer. And so, it's not designed as an efficacy study or really to establish definitively how effective this is. But, having said that, at least our first 2 participants that I know their outcomes very well are doing extremely well from this surgery. And our participant has actually been seizure free for almost a year now.11:47 Torie Robinson
How frequent were the seizures before?.11:49 David Spencer
Yeah, so they came into the study having a mix of different seizure types, but, you know, between 8 and 15 per month. So, it's really been dramatic.11:49 Torie Robinson
What's the next stage of your research? Like what will happen next?12:01 David Spencer
The next stage would be a small study that's focused more on efficacy. So that's slated probably to begin in 2025. Once we kind of get through… the planned analysis was for 10 people looking at safety, primarily. And so, once they get far enough out to ensure that the safety looks very good, the next stage would then be a larger group looking at how effective it is.12:32 Torie Robinson
It sounds like everything's moving rather quickly as well.12:35 David Spencer
It is happening slowly but quickly - both at the same time! So, we're trying to be careful to temper our excitement. There's, you know, a history that goes back - there was a lot of work done in cell therapy for Parkinson's disease 25 - 30 years ago. It was extremely exciting at the beginning. They ran into some problems. Some of their bigger trials then didn't establish that it was as effective as it looked like initially, but that a lot of that work led to this, that to develop the technology that allowed us to pursue this for epilepsy. And then there's now a definite resurgence of this work in Parkinson's again, and some very encouraging early results from those more recent Parkinson's studies too.13:24 Torie Robinson
So, I guess, be excited but don't be too excited because it's science and you never know.13:28 David Spencer
It's a trick, but we don't want to oversell it until we really understand the bigger picture.13:33 Torie Robinson
Thank you so much to David for sharing with us his exciting research into treating temporal lobe epilepsy using stem cells!
To learn more about David’s research into using stem cells as a treatment for temporal lobe epilepsy (with, Neurona Therapeutics), check out the links below this recording.
If you haven’t already, don’t forget to like, comment, and subscribe, and see you next time! -
00:00 Intro
00:48 Meet David
01:44 David's research foci
02:21 Cell therapy - implanting the cells into the seizure-focus of the brain!
03:51 What type of cells are used?
04:25 Surgical implantation of cells
04:38 Turning stem cells into brain cells
05:59 Current stage of research
07:05 Stem cell implants in people!
07:35 Outcomes in humans so far!
08:38 Benefits of cell therapy vs resection or laser ablation?
10:51 Impacts of treatment?
12:00 Next stages of the research
13:35 Conclusion & thanks
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David Spencer, MD, is a neurologist, epilepsy specialist, and professor of neurology at Oregon Health & Science University (OHSU) Comprehensive Epilepsy Center, USA.
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OHSU: david-c-spencer-md
OHSU people: people/david-c-spencer-md
Neurona Theraputics: neuronatherapeutics.com/nte001/#purpose
AJMC: how-an-investigational-cell-therapy-for-epilepsy-could-help-patients
Publications: david-spencer
New book: navigating-life-epilepsy-new-book
Medpage Today: Exciting Early Results With Novel Cell Therapy for Focal Epilepsy