Advancements in Stem Cell Research for Drug-Resistant Epilepsy - Patrick Kwan, Monash University, Australia
Learn of exciting research into a drug screening platform for personalised medicine for the epilepsies - through adult neurologist and researcher Patrick Kwan; head of the Kwan Lab! Patrick describes the process of extracting stem cells from blood, culturing them, and using them to develop new treatments for drug-resistant epilepsy. The conversation highlights the importance of collaboration and data sharing in epilepsy research.
Reported by Torie Robinson | Edited and produced by Carrot Cruncher Media.
Podcast
-
Torie Robinson
Fellow homo sapiens! My name is Torie Robinson, and welcome to, or welcome back to: Epilepsy Sparks Insights.
Still, 30% of people with an epilepsy aren’t able to control their seizures with medications, and, too many people who do have their seizures controlled with the drugs experience awful side effect. Plus, then, there’s the morbidities like depression, anxiety, movement disorders, cognitive deficits, and more, which can be equally - if not even more - negatively impactful upon a person’s life than seizures. So, we need researchers to help us find something better.
So most of us have heard about stem cell research - but did you know that we have scientists studying human organoid cells - derived from our stem cells - to work on improving treatment outcomes - for, pepole with an epilepsy? And, tis is what we call workign on personalised medicine!
So, I’m excited to be chatting today with consultant neurologist and researcher Patrick Kwan from Monash Uni in Melbourne - who can share with us a snippet of his research into the aforementioned!
Please don’t forget to share your thoughts on this episode with us in the comments below - I enjoy reading your thoughts and responding to them! Do subscribe so that we can educate and empower way more people affected by the epilepsies around the world, and, indeed, more clinicians with patients who have an epilepsy - to provide the best care possible.
Patrick Kwan
I'm an adult neurologist. I guess my day job is to treat patients with epilepsy, but I'm also a researcher. I'm a professor at Monash University. And I also where I do a lot of research into finding ways to improve the outcomes of people with epilepsy using a variety of techniques from both in laboratory base, also looking at clinical data and even looking at health services, health economics. My other hat is I'm the co-director for Monash Institute of Medical Engineering, which is a platform within Monash University to promote and educate and train people to do research to bring medical technology solutions for unmet clinical needs. So, it brings together 4 different faculties: medicine, engineering, IT, and art and design.
Torie Robinson
Art and design, that's cool. Well, I guess that is an important part when designing something, isn't it? It's got to look swish enough and function. So, you've got multiple projects, but you're doing some work with an MRFF grant into stem cell research. How? Stem cell research? Epilepsy! Tell us about that.
Patrick Kwan
Yes, so it's obviously a very exciting new area as a research tool, stem cells. And nowadays, you can grow stem cells from just a tube of blood. It's much easier now. And the stem cells, once the blood cells are converted into stem cells, they can be changed to different cell types of interest. And our interest in the lab, obviously, is around neurons or brain cells. And we use that in several ways, in particular, using as a disease model. So, you can use that to model that person's individual's disease. But also using this as a drug screening or drug developing platform or method to screen different drugs. And the uniqueness I guess of stem cells is that it retains all the genetic material of that particular individual and we're all different our DNA sequence is all different but when it comes so the stem cells would retain all of that information so if we use that as a way to as a model of that particular person's brain or how they will respond to medications then it becomes a really personalised system.
Torie Robinson
Personalised medicine.
Patrick Kwan
That's right.
Torie Robinson
And so, what's the process of this? You take, you literally have a, some, human blood and you're in your lab. What actually happens?
Patrick Kwan
Yes, obviously we explain the research, what it's all about to the person and they just take a drop of blood just like when you go to see your GP: you take several mls of blood and we take that to the laboratory and then we extract the white blood cells, we remove all the red blood cells and from the white blood cells they can then be cultured and then reprogramming. We reprogram them backwards if you like; turn them back into stem cells. That process takes several weeks and we do that in the laboratory, put them in the incubator, there's a culture, and after a few weeks - when they are stem cells - then we can treat them as, like, in the very embryonic stage. You can turn them into whatever cell types: [the] types of cells we're interested in. And that can take - for nerve cells - that can take between 4 to 6 weeks. And the cells then become active. We can see the activity, what we call firing. We can see spikes when we measure on using electrodes. We can pick up the electrical activities. So, it's super exciting and they're beautiful as well, I must say. They're beautiful to look at under the microscope.
Torie Robinson
Really? What do they look like - if you can describe that?
Patrick Kwan
You can see strands of nerve cells with strands how they are connecting to each other. That really is a model of the brain, because as you know the brain is a network. All the different brain cells - they are connected in different ways - they're different cells as well. And we can stain the cells with different colours as well. So, it's a beautiful, beautiful picture. More like a starry sky at night.
Torie Robinson
It sounds fascinating how you've got these human cells and you've well as manipulated them and they're still around weeks later. How do you keep them alive for so long?
Patrick Kwan
Well, yeah, you have to… just like [with] people, feed them well, give them warmth, and grow them for weeks or months, and they, over time, they actually turn into little balls as well. So, we call them organoids. They become a 3-dimensional little ball - almost like the size of a grain of rice.Become a 3-dimensional little ball - almost like the size. So, we can study them either in a…what we call a 2-dimensional way; that's just a sheet of nerve cells or 3-dimensional (depends on the purpose of the research). And what is even more fascinating, I would say, Torie, is that the… you remember that the stem cells we reprogram from the original blood cells, those stem cells - we can store them forever - as in we can freeze them in the freezer and they're kept forever! So, whenever we need to have some more nerve cells to investigate for that individual, we can just thaw them from the freezer and grow them up into nerve cells again. So, it becomes almost like an infinite source of materials or cells for us to investigate for that individual!
Torie Robinson
Do they not become damaged when thawed and frozen and thawed and frozen?
Patrick Kwan
They're pretty resilient. We have to look after them well. The mini-me's live on!
Torie Robinson
It's like they're pets or something these human cells!
Torie Robinson
And what particular type of epilepsy using this are you researching using these cells?
Patrick Kwan
Yeah, and so, as I said; because these cells keep all the genetic material of that person so naturally you would have thought it'd be most relevant for people with the genetic form of epilepsy - and that's some of the focus we have been with this grant - is to recruit people with genetic causes (with known genetic causes) of epilepsy. As you know, there many genetic causes now - often they disrupt how the signals are transferred or between cells. What we call the ion channels, when there's a firing of the nerve cells, it's because of signal changes. These are the patients we particularly target, genetic epilepsy. And because we know the genetic mutation that causes the epilepsy, what we can also do nowadays is with a technique called CRISPR, you might have heard about it
Torie Robinson
Oh, yeah!
Patrick Kwan
…to correct that mutation, put back a normal sequence of the DNA. So, that allows you to compare and you understand exactly what the mutation has done to the behaviour of the nerve cells.
Torie Robinson
So, you're taking a cell from somebody who might have say, I don't know, Dravet Syndrome or something…
Patrick Kwan
Yes, yep.
Torie Robinson
…then you process it in the way that you've described, then you have your, what would you call it again?
Patrick Kwan
Well, they called iPSCs, Induced Pluripotent Stem Cells, or iPSCs for short.
Torie Robinson
Okay, okay, and then you can edit that cell can you to make it seizure free…
Patrick Kwan
Yeah, yeah!
Torie Robinson
…or you can use it to…
Patrick Kwan
Correct! Yeah, we can edit the cells, edit. So, we correct the abnormal DNA sequence. We correct the mutation.
Torie Robinson
That's pretty swish. That is pretty cool. But this, of course, these are little cells and they're not... Do you use rodents yet or at what stage are you?
Patrick Kwan
So, the cells, yeah, you're right. I mean, these cells are still just cells cultured. So, they obviously they don't represent the whole, the entire complexity of the brain, but then they are good platform. This is a good platform because they're very safe. You know, if we treat animals or even people, whatever intervention we give - that may cause harm. So, these are cells, you know, we don't have to worry too much about safety and it allows us a lot of high throughput screening and testing. So, we do a lot of testing over a short period of time, whereas it will [sic] be very difficult, even animals and people, let alone people. And so, once you use it as a screening test, once we screen some candidate drugs (for example), then we can take them onto the animals and eventually to the patients.
Torie Robinson
And where do you think you…do you foresee… in a couple of years, in 5-10 years - potentially - you furthering this research to go into animals? Or you can't say yet?
Patrick Kwan
Well, that is the goal. So, right now we have one of the projects that will receive MRFF funding is to use this in vitro cell system; to screen for a new class of epilepsy that currently doesn't exist.
Torie Robinson
Aha!
Patrick Kwan
Then, when we’ve done the screening, then we will test on animals. And the next stage would be to test on people.
Torie Robinson
Do you have any numbers/statistics that you can quote in regards to your research here?
Patrick Kwan
Yeah, mean, we were trying to help the 30%/one third of people with drug-resistant epilepsy. That's the main driving of our research. You know, 30%, even now, within the last 30 years, more than 20 new drugs have been developed, one third of people are still having drug-resistant epilepsy. And the different methods to tackle that: I've mentioned stem cells as one of the personalised ways. The other way we're doing is applying AI to help us select the right medication by learning from large patient databases how patients responded to existing drugs and that may help us to choose the best medication for that particular individual using AI.
Torie Robinson
My goodness, you're just sending my own remaining brain tissue wild in wonder; just thinking about all the potential options of the future. And this work just shows data is so important. So, I guess the more of us that can be involved, patients and clinicians, the bigger our data set and the greater the likelihood, fingers crossed, of finding improved treatments for the future. Would you agree?
Patrick Kwan
Yeah, absolutely. In fact, the research communities in epilepsy, we're all very collaborative. We all support each other. And the AI work I mentioned: we set up an international network of centres contributing data for us to train our AI model. So, we now actually have data from more than nine countries, more than 20 centres for us to train and test these models. It’s very exciting; data from across… for thousands of patients. But we need… the machine is hungry(!), as they say, the machines are hungry, so also, we are very grateful to the patients who have allowed us to use the data.
Torie Robinson
And wouldn't it be really useful - or it's almost essential (I think) - to get a greater diversity of patients involved as well? Because it tends to be (I mean, I'm generalising)… but there tends to be a certain type of person who goes forward for research all the time, but we need to, I think… I have a passion for getting more people from different backgrounds involved. What do you think?
Patrick Kwan
Absolutely, yeah, yeah, I that is one of the often criticisms for… you AI is very narrow and...you know, we don't have enough diversity; so, absolutely. We always, in our work… that's what we make sure we cover: people from different backgrounds, different socioeconomic settings, from different countries, from different continents, to ensure that diversity, and [so that] what we find can be more generalisable, [and] can be applied to people with different backgrounds.
Torie Robinson
Yes, we are all the same species after all, you know, so, okay, lovely. Well, thank you so very much, Patrick. It's been lovely to meet you finally. And everyone; keep an eye on Patrick because he's doing such amazing work and you'll be presenting at the…
Patrick Kwan
The American Epilepsy Society. Our team will have a few presentations there. So, look forward to seeing some of you there.
Torie Robinson
Thank you so much to Patrick for giving us a glimpse into his research - and making it fun and understandable! Check out Patrick’s papers and more about is work on the website torierobinson.com (where you can also access the podcast, the video, and transcription of this episode), and if you haven’t already, don’t forget to like, comment, and subscribe to our channel, share this episode with your friends/colleagues/family members(!) and see you next week!
-
Patrick is a Professor in the Van Cleef Centre for Nervous Diseases, Department of Neuroscience, within the Central Clinical School, and Consultant Neurologist and Head of the Epilepsy Clinic at Alfred Health.
He is a medical specialist in neurology and an international authority in epileptology and anti-seizure drug development.
Patrick’s research portfolio encompasses both applied basic science and clinical aspects to improve the treatment outcomes of epilepsy. His research is focused on understanding the effects of long term treatment, identifying factors that affect outcomes, mechanisms of drug resistance, identifying novel molecular targets for the treatment and prevention of epilepsy and translating research findings into the practice of personalised medicine for epilepsy.
-
X/Twitter: patrick_kwan
LinkedIn: patrick-kwan
Kwan Group: kwan-group
Monash Uni: patrick-kwan
Alfred Health: prof-kwok-kwan
Malvern Neurology: patrick-kwan
Scopus: 7004369601
ILAE: patrick-kwan
ResearchGate: Patrick-Kwan