MS Tissue Bank – Information Talk – Dr Djordje Gverik | MS Society


Now there’s lots of unpredictability in
MS, but there is one thing, we’re all going to die. And what we need you to do
is leave your brains to George. And he’s going to explain why. You’ve seen some
reasons why from Klaus, and I’ll let him take it away. Right, thank you. So I’ll be
as quick as Rod so, because I don’t want to delay lunch any further, and most
of what I’m gonna tell you about the brain bank is sort of behind the scene
work that we do, is on our website, so the information is there. All you need to do
is just note down the website address. So to move on, the main aim of
the brain bank is to facilitate research and to facilitate it using the most
relevant material for that kind of research into a MS, and that’s human
brain affected by Multiple Sclerosis. Our name says a few things about us. Multiple Sclerosis Society because we have been supported now for more than 30 years by
the MS Society. Tissue, because we collect brain spinal cord but also other tissues
that might be relevant for research, including muscle, gut and some other organs and tissues. And Bank, because we house some very, very
valuable specimens there, because they they actually help us explain MS and
what’s going on in MS. We work with many people, our donors and relatives are
obviously the most important group of people we work with, providing tissue,
providing information. We provide feedback in the form of a Neuropath
Report, if people are interested to learn about these things. And also we can, in
the future, provide some of the genetic information when we do studies on our
cases. For researchers, we’re a source of tissue and also quality assurance and
expertise of working with human tissue, because that’s not the simplest thing
to do. We educate health professionals and anyone else who wants to learn on
what’s really going on in brains of someone with Multiple Sclerosis. And then,
the most important one these days for us is MS Register. And we’re trying to link
with this wonderful resource with the source of information, because the
quality of tissue at the end of a day, depends of the
quality of data that accompany that particular sample. The donor scheme is UK-wide and we’re quite proud to be one of these rare, actually the only brain
bank that is that is UK-wide, has a UK-wide donor scheme. We collect their
issue from Orkneys down to Guernsey and Jersey, so anyone is welcome to donate
tissue, to register on the database. And the one good thing about is that we
are not biased in any way, which means the samples in the brain bank represents
what’s going on in the MS community in the UK. And if you turn it into the fact
that we supply tissue worldwide to absolutely anyone who’s interested in
doing anything, researching any aspect of MS, then whole of the world is
researching the UK MS. So the benefits are there, probably in the future and
already happening. We’re trying to raise awareness about MS and about the importance of brain banking and this is one of those events where I’m trying to
persuade you to consider donating your tissue when the time comes, to our brain
bank. As I said anyone can donate tissue, those with Multiple Sclerosis, but also
controls, people who are related to someone with MS or those who don’t have
any connection with MS. They’re so called ‘healthy controls’. Again, I have to stress
please consider joining the MS register first, donate your data, because that will
help us actually make this tissue even more valuable. Donating, actually
registering on the donor scheme is a straightforward process. All you need to
do is either go on our website, which is up there, in the corner. And you can
either download all the forms or you can just ring us and we’ll send you all the
forms with a free post envelope which makes it easier to send it all back. And
after that you’ll get a standard donor card which will have your name and the
donor number and you can carry that with you or can you just decide to leave it aside for a while, until it becomes relevant. The actual tissue retrieval is
a very streamlined process and the most important fact to state
here is that we do it all, so there is no additional burden on the family. There
are no additional costs or anything like that. We will organise absolutely everything from death certificate to collecting the
tissue, bringing it down to London in our lab. All we need is someone is to let us
know that a donor has passed away. That’s probably the most important thing and
that’s how we you lose those cases that that we cannot retrieve. The other
important fact is that something like this can be done within a very limited
period of time, which is up to 48 hours. And a lot of what’s going to happen
later on with the tissue depends on the post-mortem time and also some other factors that happen around the time of death. The tissue preparation is
probably the most important part of what we do. And this is the preservation of
tissue rather than just preparation. And this is to stop further damage to
the brain and to preserve it in some kind of a state that you can encounter
in a living person. That includes a lot of different things but most important
one is actually that we have specific grids on which we put these brains and
take some pictures. Then we cut along these grid lines. Generate on all these
samples, about 250 samples from every individual brain and spinal cord. And
then later on we can go back to our images and identify absolutely any part
of the brain that’s necessary for researchers or any pathology,
specific pathology that’s relevant for that particular project. And some of
these areas that are quite interesting that helps us further the research, is
something like an area called hippocampus, which harbours stem cells in
the brain. So a lot of people who are investigating the role of stem cells in
MS and any other conditions, especially in neurological conditions will
ask to see an area that harbours, that contains hippocampus. And in
our case that would be probably D4. If you look at it, it’s a small convoluted
fault in the brain. So the samples can be kept frozen, which is the best
way to preserve human tissue, because we can use it in all these wonderful
techniques that we have these days, called ‘omics’, so proteomics, genomics. This allows us to essentially look at fifty thousand, hundred thousand-plus data
points at the same time. And we’re using a very small amount of this tissue, so we
can be very precise when we look at the tissue where the problems are and what’s
actually going on in these bits and pieces. This is probably the most
important thing when you think about human tissue and how relevant it
is. And it’s, it is that any piece of tissue that we have, any brain that we
have, has all the factors that are playing role in MS, contained in that
little bit of tissue. The main problem obviously is to find what’s in that tissue. To find the techniques, how to unravel the all these
secrets that MS has had. And we treat it as a sort of a scene of crime, you can
think of it as that, and we’re trying to find all the evidence or using all the
available techniques that we have these days. This is a very serious process, very
occasionally slightly lengthy process in which we’re trying to actually come up
with a final classification of all the tissue samples. So every single brain
sample that we take, so all 250 will go through the same process. So we will
eventually come up with the neuropathology diagnosis, which I have to
say almost in 99.99 percent of cases corresponds to clinical diagnosis or
diagnosis of MS is not a problem anymore. And we don’t find anything really that
is sort of on top of MS there, apart from some other cases where we have
all the people, when there are some aging pathology present, or problems with blood
vessels and so on. So all the lesions will be then classified into those that
are very quiet lesion, so those scar tissue which is on that side, over there.
Or those kind of more inflammatory lesions which are kind of more and on
this side. And this is where science comes into play. So most of the
scientists are actually all of the science usually relies on extremes.
And the logic behind it is that if you have an extreme situation, whatever is
going on in that particular condition will be represented to sort of a higher
level. We’re quite blessed that we have, we sort of covered both of the
extremes in MS. On one side we have people with benign MS who will be going
for many years. 30, 40, 50 years with very few problems, occasional relapse,
very little progression, very little disability. Now tissue from these people
is very interesting because we’re trying to find out what makes them resilient to
to this mainstream MS, and we have a large number of these samples. However, as you all know, all your DMTs are still working on the inflammation and immune
system and consequently a lot of scientists are still interested in
inflammation in MS or in the role of the immune system. And we need more of
these inflammatory samples. And this is why I always try to stress that we, we’re
looking for people with a very progressive condition, very aggressive MS.
iI they’re willing to join our donors scheme and donate tissue when the time
comes, because we assume that whatever is causing a mess might be present in much
larger amounts in their brains rather than in those people who have a sort of
a standard form of MS, just a secondary progressive or relapsing
remitting one. So to just go very quickly about pathological mechanisms, because
this is behind all the drugs that are being prescribed to people with MS. So
the first one that’s been around for many many years is inflammation and this
is the one that’s been tackled by the DMTs. So we can successfully tackle the
inflammation in MS. As you’ve heard before from Gavin and from Klaus, to some extent, inflammation is there because something is going on. So in my personal
belief, inflammation is usually a good thing, because if you look at it
inflammation is something that will bring on the repair. So they actually, the solution to the problem. What’s going on with the
inflammation in Multiple Sclerosis? There is something that’s going on but
ultimately we think that inflammation is probably the good one so it needs to be
redirected in the right to along the right pathway. And we know quite well that cell that is considered the most important in
MS pathology, it’s a scavenger cell called microglia macrophages. They’re
very versatile and they actually respond to the signals from the environment.
Which means if these cells are told that for instance, neuronal cells are hungry,
they need some kind of support, they’ll start pumping out factors such as nerve
growth factors that actually support survival and function of neuronal cells.
If these cells are actually told that something is wrong there, and they
basically just need to go in like a bouncer and get the stuff out of
it. They will go in, they’ll attach themselves to the myelin sheet and they
will strip the myelin off and remove all the stuff that might be causing problems
in MS. So this kind of cell is probably the main target of all the old
MS research, so microglia or macrophage. Closely linked to inflammation is
demyelination or loss of myelin and then also remyelination,as a process of
repairing myelin. Now this is where drugs work in form of a secondary effect. So if
you stop the inflammation you will actually stop the demyelination or you
will enhance the remyelination. So we have tackled these two processes quite
well. Now there’s one that Klaus has been talking a lot about and that’s the neuro
degeneration in MS. So this is the advanced MS, when we have actually loss
of neuronal fibers and consequently loss of neuronal cell bodies. And we see that
neuro degeneration is something that cannot be stopped at the moment, is still
an underlying process and it will go ahead despite of the number of drugs
that someone can take to tackle the inflammation and demyelination. And this
is something of a more recent finding in MS. It’s been recognised for many years
but has received more attention, more recently. And when we talk about neuro
degeneration you probably think about Alzheimer’s disease, you think about
Parkinson’s, not always of MS. So the view of MS, from the point of pathology, is
changing and we are kind of identifying different mechanisms that we
need to tackle in order to bring solutions for people with advanced MS,
for more people who have a lot of scars in their brains, and so on. And just briefly to mention two more mechanisms that might be
playing role in MS, one is mitochondrial damage. Now this has been floated a lot
in many different conditions. This is all down to the energy production. So
that the function itself, energy producing part of the cell called
mitochondria and essentially important because we can now start thinking about
drugs that can actually tackle this kind of problem, together with the oxidative
damage which has been revisited a few times before. And it’s all down to
these antioxidants that you’ve heard a lot about. So all of these together now
forming a new path towards a cure of MS, towards a new way of treating MS, by
tackling not just inflammation and demyelination. We are now moving into
neuro degeneration and hopefully, with some drugs that can be repurposed
from some other conditions, we can tackle mitochondrial damage and the oxidative
damage in brain. So going back to what we are really set up to do, is to support
research. As you can see from the map we have reached any part of the world
where there is MS research going on. We’re supplying tissue to Australia most
of the Australia has a very strong MS research field, North America and any, as
I said, any other place. And we’re covering absolutely anything that’s of
interest in Multiple Sclerosis. Anyone with a bright idea of looking at what’s
going on in MS will, come to us at some point. Why is this important?
As I said, we have MS tissue is the most relevant material on which you can
do your research. It’s not the easiest material to do it and that’s why we have
different other things, we have models, we have cell models, we have animal models
and so on. But it’s advisable that at least once during your research project
you go to MS tissue and you actually validate your findings. You find out
whether something you’re looking at, whether your protein, your gene that you
found in a dish or in an animal, is actually relevant to someone with
Multiple Sclerosis. And all the factors that cause Multiple Sclerosis are
present in the brain of someone with MS. And I’ll just
give you quickly a few examples of how we use tissue for research. So these are
the, just three there that I’ve sort of highlighted. So the first
one is improving diagnosis and Klaus has done some of this. They essentially were
taking brains which are formalin-fixed. They’re quite easy to handle which means
they can be imaged in an MRI machine and we can produce same images as with the
patient’s. Difference is that we can do histology which is a very simple thing
to do. And it gives you a very high degree of precision when looking at
different pathological changes. So we can look at things that MRI can see easily
but also at some features, pathological features that cannot be
seen on MRI. And in this way we’re not improving just diagnosis but we can also
in some way improve clinical trials which rely on MRI as one of the outcome
measures. We’re also supplying tissue to variety of studies looking at biomarkers
and these are the ones that if you want to prevent MS, you will need a biomarker.
You will need to recognize what might be happening in MS and whether someone will develop MS. So there are a variety of molecules, proteins and so on, that might
be relevant in Multiple Sclerosis. So these are the type of studies that are
quite frequently cropping up in our tissue requests. Looking at repairing
damage using some sophisticated techniques like isolating single cells
from a bit of a brain, then looking at a genetic profile of that single cell. This
is another thing we can do and it’s done on a very, very small amount of
tissue. And in this picture, essentially what is shown, that you can sample the area that’s already damaged, which is the white area
there, so there’s no myelin there. You can sample the area that’s being repaired,
this is the pale blue shaded area, up there. Or you can sample the normal white
matter. So normal myelin in there. So you can look at all those three, which are in
very close proximity, and you can find the fine differences between these and
you can come up with conclusions. What’s driving the actual remyelination? What’s
driving scarring in MS? And what’s actually preserving the white matter
that hasn’t been affected by the process itself. And finally what we have
developed in a lab sort of more recently, based on some work from other
people, it’s a technique called ‘fast clear’ and this allows us to
basically make brain tissue transparent, and then do some staining and create
these 3D models of human brains, of human blocks, in which we can observe how these
scavenger cells actually interact with their target, with neuronal cells and we
can also look at how neuronal cells communicate with each other through
synapse is and how these synapse, which are important for exchange of
information between neuronal cells, are they damaged in Multiple Sclerosis.
So this is something that we’re currently developing and we’re hoping
that hopefully there will be a study coming out soon, but as a brain bank this
is a part of the service that we provide to our researchers. And finally just to
show you our website. So as I said, most of the information about, all of the
information is there, if you’d like to download the forms, if you’d like to read
about the research, if you like to see who we are, what we do. It’s all there and
that’s all I want to say, so thank you and let’s go eat, I guess.

3 thoughts on “MS Tissue Bank – Information Talk – Dr Djordje Gverik | MS Society

  1. This is amazing, i would love to be a part of this. The more we give, the more information people can find out and we can beat MS once and for good 🙂 I would love to go to the MS brain bank and spread their work through my Youtube channel!

  2. The brain bank is fundamental to understanding this terrible disease. Highlighting the cause is so important.
    But the camera work on this video was horrendous!
    Also, give us a link to the brain bank.

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