“The story on MS is still not written…There’s so much more we’re learning…If you look at the history of MS over the last 20 years we’ve seen wave after wave after wave of innovation, and you have thousands, tens of thousands of researchers dedicating their lives to finding a cure for this disease, finding better therapies for this disease, so I would say the odds are in MS patients’ favour, more now than ever.”
Dr. Vas Narasimhan. CEO Novartis. January 2017.
What is MS? Breakthroughs in understanding and treatment.
Making the film I spoke with leading researchers, scientists and doctors. Only part of their interviews could be included in the edit. Informative, enlightening and inspiring, their contributions to the film are transcribed in full here:
Dr. Vas Narasimhan: CEO Novartis: MS and breakthroughs in treatment.
Statistics 2020
Dr. Vas Narasimhan. CEO of Novartis on MS and breakthroughs in treatment.
Transcription of filmed interview with Elizabeth Kinder
9.25. So, Vas. I think there are 3 types of MS. Can you tell me what they are?
9.27. There are three types of MS. One is called relapsing remitting and this is the most common diagnosis of MS and the one that most patients start out with. It starts out with some problems with your walking with your co-ordination, you might notice some fatigue, some other symptoms and what you notice is really typical of this type of MS is that it relapses and then it gets better. People start to feel better and then they have a relapse. What we’re always trying to do is get people to stay better for longer.
9’57. Now over time once patients have this relapsing form for many years they (can) develop something called secondary progressive MS, that’s when the disease starts to progress consistently and doesn’t actually get better, it just continues to get worse. We think why that happens is that the disease has really gotten into your brain and your central nervous system and that’s a much tougher form of the disease to treat.
There is a 3rd form, which we think is a completely different form of the disease. It’s called Primary Progressive MS. This is a disease where right from the start, patients are just getting continually progressively worse over time. It’s really the most severe form of MS.
EK Isn’t it true that two thirds of people diagnosed with MS are female?
VN Right
EK But that men if they’re diagnosed tend to get the worst case, the Primary Progressive.
VN. They do. We understand the least about Primary Progressive MS.
EK My friend AL was diagnosed with Primary Progressive MS, 24 years ago.
VN That’s amazing.
EK Is there any hope for him now, is there anything that could be done?
VN First of all it’s incredible that Al has been able to live such a wonderful life for 24 years since his diagnosis. That’s really a testament to his will and determination.
There’s really a lot of research ongoing and a really important breakthrough with so called ‘B’ Cell based therapies. Which are targeting a different part of the immune system that looks to be very promising. Right now it’s undergoing regulatory review, but these kind of b cell therapies look to be able at least to slow down the progression of Primary Progressive MS and I think that’s the beginning of what I hope will be a much longer story about conquering Primary Progressive MS.
EK . So what is ‘B Cell’ therapy?
VN So what these drugs do is they prevent b cells, these are the cells that produce antibodies, antibodies are the ones that protect you normally from infection. But in MS, particularly in Primary Progressive MS those B cells are attacking your nervous system and also activating other parts of the immune system.
So the thinking is if we can suppress those b cells or eliminate those b cells from the body, can we slow down the progression of Primary Progressive MS? Of course we have to watch out for infections and other side effects. But it at least has the potential to slow down the progression of this disease.
EK. Brilliant and does that also cause re-myelination?
12.19 VN That would be our hope, that would be the dream to actually get re-myelination. It’s very hard to demonstrate that re-myelination is happening. We don’t know yet if these drugs are actually having that effect, but if we could show that, it would mean we are actually reversing the process of the disease and that would be very exciting.
We work a lot with the patient community, with MS researchers to constantly look for new ways we can improve patient care in Multiple Sclerosis. Because there’s a lot that we still don’t understand. We don’t understand what causes the disease fundamentally, we don’t (necessarily) understand why these drugs are having the effects they are. We have our hypothesis, we think we know, but we’re always trying to learn more. We’re really trying to be very open with our science and open with our collaboration to really advance the care for MS.
EK (Good) And the myelin sheaths are the ones that protect the nerves, creating a coating, like plastic over copper wire…
VN That’s right, exactly. The Myelin sheaths coat the nerves all around your body. And what they do is allow the nerves to conduct the signals that allow your muscles to move, that allow your body to move, allow your brain to think. What we know about MS is that the immune system is attacking those myelin sheaths. That’s impacting how the immune system is working. In all of these therapies, what we’re hoping to do is protect those myelin sheaths, hoping as you said to get them to grow back that would allow the nervous system to proceed as normal.
13’25. EK If the sheaths grow back does that mean the nerves regenerate, is that the theory?
13’28” VN Let me think, how best to answer that.. If we can get those myelin sheaths back, we certainly know the nerves will conduct better. In terms of nerve regeneration that’s a much longer time period to actually see that happen, so it’s much harder to evaluate.
But that would eventually be the hope.
Can we figure out a way to not only protect the myelin sheath but actually eventually get these nerves to regenerate and reverse the trend of the disease. But we’re a little bit away still from that.
14’01. EK OK. So I”ve been diagnosed with relapsing remitting MS,
VN Yes
EK So theoretically I’m facing secondary progressive MS, which is the same as primary progressive MS, in that there’s a steady deterioration, there’s no remission. So for me, what hope is there for me should I get to that stage? And what’s the likelihood that I will?
14’30 VN First I feel optimistic. When you look at the history of MS 20 years ago we had no real therapies for MS. Then we discovered the interferons, we discovered glatiramer acetate, copaxone, and suddenly we have four or five therapies for MS. Then with fingolimod we suddenly realised we could affect T- cells and we had a whole new slew of therapies for MS. Now we’re learning about B cells and more therapies are coming out for MS.
15’01 So the story on MS is still not written. I think there’s so much more we’re learning. We don’t know exactly what makes patients progress from relapsing remitting MS that you currently have to secondary progressive MS, but we do know that a reasonable proportion of patients will eventually progress. What’s interesting is that Novartis has run a trial on Secondary Progressive MS and we’ve shown for the first time an impact on the disease, we don’t know yet, how we’ll take this forward.
15’33. We’re discussing this with regulators, but it was the first time you could show that you could reduce relapses in secondary progressive MS, reduce lesions on your brain scans that you see with secondary progessive MS and I think it shows the possibilities there are in this area and (the need for) more studies to find better therapies.
16’ EK. That’s amazing. But presumably you need to get effective treatment early.. when Al was diagnosed, no treatment available and now there’s a much better outlook.
16’14”. VN The great thing about your story is that you’ve had ten years of being on therapy. Probably the disease has not had as much opportunity to damage your nervous system given that you’ve been on steady therapy for all that time. We don’t have great studies to show how these more recent drugs have impacted the patients who are progressing to secondary progressive MS, but it’s certainly our hope that if you’ve been on ten years of a therapy that’s really helped you symptomatically, that maybe that’s reduced the likelihood that you’ll get the secondary progressive MS. That would at least be the hope. We will continue to work hard on our side to develop better therapies.
16’55. EK Well thank you!
EK MS is on the increase across the world in populations where it was previously unknown. Do you have any idea why this is? Or what triggers it?
17’07 VN We don’t know what triggers MS, we know it’s a combination of genetic and environmental factors and there are many different theories, but I don’t think there’s been any sound evidence to tell us exactly what’s causing MS. I personally believe that what’s leading to increased diagnosis around the world is more recognition of this as a disease, and probably in many parts of the world where there wasn’t a lot of testing or awareness that patients needed to be evaluated, that’s happening more and more we’re seeing MS rates go up. We’re perceiving them to go up. All we’re really doing is identifying all of the MS patients that were always there.
17’44 EK Oh Right. How do you think you could find a trigger? Is there any theory about why this happens?
17’52 VN There are many theories. Some say viral infection could be part of the story; some say certain environmental factors. It’s very complex to work this out. My guess is that it’s many different stories, depending on the genetics of a person, depending on the environment that they live in; there are probably different elements that are leading this disease to actually start up. There will probably never be a clear answer to what’s causing MS.
18’23 EK I suppose that’s because everybody’s immune system is unique to them. And so they’re going to react differently to their environment.
18’30 VN Everybody has a different genetic makeup. Everybody has a different environment, everybody has immune systems that we say are primed in a different way and that means that there are a lot of factors that actually lead to an autoimmune condition arising like MS.
18’46” EK You just mentioned there about genetics and I want to know what the genetic implications are. I have an 18 year-old daughter and I’d be very keen for her not to get it.
18’58” VN What we know about MS is that MS is not a hereditary disease, it’s a disease that really arises based on environmental and genetic risk factors. We don’t have any genetic testing for MS either, so it’s very interesting. We sometimes see MS can be part of a family history and sometimes not. I think what’s important is that we do early diagnosis and ensuring that patients are getting on effective therapies very early. Because I think the tricky thing with the very early stages of MS, as I’m sure you know is that what feels like little bit of loss of co-ordination, maybe some odd tingling and different feelings, might be this disease.
Often we say “oh it’ll just go away.” What’s important is that patients are educated and parents are educated so they can let their children know that they can watch out for these symptoms and then get diagnosed and treated.
20’07” EK Mm. And why is it so commonly misdiagnosed.
20’11 VN You know it’s interesting. In the early stages of MS I think these are easily dismissed as any number of ailments. It could be an infection it could be tiredness, many things that physicians don’t put all of the pieces together to think about MS. I think what’s important is that if it’s something that’s staying with a patient for an extended period of time and is really affecting daily life, you have to get a proper evaluation.
That’s where physicians really have to be aware that they may be having an MS patient in their clinic.
EK So if you are a betting man, what would you say the odds were if my daughter, hopefully she won’t ever have to deal with it, but if she did, what would the odds be on her having a cure?
VN You know, I think the odds on having a cure in her lifetime I would say are, this is a tough one…
Well first I hope your daughter never has to deal with this. I think what would be the odds of having a cure, I could say 50/50 but that obviously feels like a cop out, I think, in my heart I believe that it’s better than ever, because I think you look at the history of MS, over 20 years we’ve seen wave after wave after wave of innovation, and you have thousands, tens of thousands of researchers, dedicating their lives to finding a cure for this disease, finding better therapies for this disease, so I would say the odds are in MS patients’ favour, more now than ever.
VN You were diagnosed with MS when there was unbelievable research activity and it’s still ongoing. I think these B cell therapies will be very important.
EK It must have been so exciting to be part of that, part of that new discovery, here’s a disease that affects millions actually, How many, 2 or 3 million world wide?
VN Yes but I think it’s because it has such a dramatic impact on younger people. That’s what makes MS so unique. People in the prime of their lives are having a disease that can, depending on the stage really disrupt families and communities.
EK It’s commonly diagnosed between the ages of 20 and 40 isn’t it?
VN Yes, and depending on how fast it progresses you can have relatively advanced disease at younger ages than we find in other areas.
EK And I suppose if people are getting effective treatment early they can then, they’re able to contribute to their families, they’re able to stay in work
VN That’s right
EK and that’s going to have an impact on their mental health, their wellbeing and their sense of self worth, that’s going to be intertwined with a much better prognosis.
VN That’s right. Yes, exactly.
I would like to pick up on something that you mentioned earlier. About AL and the fact that he has had primary progressive MS for 24 years,
VN It’s pretty incredible actually,
EK And you said it was a testimony to him and his courage and humour. And so I want to know what role does your psychological health and your approach to life play in your prognosis in MS? Or any disease?
VN I think in many diseases what we know is that optimism, a positive outlook does lead to better outcomes. We don’t understand why, but there’s clearly something going on in the body where patients who have, whether it’s a cancer, whether it’s MS whether it’s any other condition, who have an optimism about their life, who are thinking about their future, who are thinking about the positive rather than the negative, of their condition and are seeing an opportunity – do better than patients who don’t.
So I think that really shows the power of the human spirit, and is probably the reason why Al has had such an extraordinary journey.
EK I’ve discovered this stuff about meditation where apparently if I’ve understood it properly, it releases endorphins, is it dopamine and other things that then impact on the cells. I was wondering if with that positive outlook you release some chemical in your body that has a biological impact.
VN Well as somebody who meditates and practices mindfulness I’m certainly hopeful that there’s dopamine, serotonin, other neurotransmitters (involved)…I think there’s been very interesting studies. But there’s probably some wisdom like the fact cultures have been practicing these kinds of mindfulness exercises for thousands and thousands of years, so I think there’s definitely a positive. Even if we don’t understand why, that’s OK too.
EK Brilliant. Well Vas, Thank you, very, very much.
VN It was fun! I think we all identify MS and when we think about the typical MS patient, we think of somebody like you. And so that is something that every body wants to fight for, a mother, a wife, somebody researchers can relate to and want to have an impact on. That’s why MS has an incredible amount of research activity dedicated to it.
EK Brilliant, Well Vas, Thank you, very, very much.
Dr. Vas Thank you so much. It’s been an absolute pleasure to meet you.
VN Pleasure to meet you as well. Thank you.
Tony Dow, Director. Thank you very much indeed.
I was riveted.
Stem cell Therapies. Promising breakthroughs in MS treatment
Anna Williams:
Professor of Regenerative Medicine. Ann Rowling Neurology Clinic at the Centre for Regenerative Medicine Edinburgh.
AW. My research group is particularly interested in a process called re-mylenating. We know in MS that myelin (that forms the protective sheath around the nerves) comes off the nerves. (So the nerves can become damaged and the signal impaired). And what we’re trying to do is understand how the repair works.
AW So what we know with this, is that in all of our brains we’ve got cells which we call stem cells. We also call them oligondendrocyte precursor cells. Oligondendrocytes are the ones that make myelin and they then wrap the myelin around the nerves. If myelin falls off these oligodendrocytes precursor cells get attracted to the area of injury and they start to form new myelin that wraps around these nerves. And this new myelin is good because the myelin is there to help the nerves conduct electricity, but also it’s there to feed the nerve.
AW So this stem cell has two roles:
It can repair the damage if the myelin falls off.
It also keeps the nerves alive.
We think this is really important in the later stages of MS. When people get a bit of disability that doesn’t go away, we think that’s because the nerve’s died. So re-myelination is trying to put the myelin back on the nerves to keep the nerves alive.
EK SO if there’s actually been nerve damage done and you’ve got constant symptoms of one sort or another will the myelin then repair that damage?
AW So that’s what we hope. If we’ve got a nerve that has lost it’s myelin, and that’s why you’ve got your symptoms, if we can put the myelin back, that should
improve your symptoms.
Even more importantly perhaps in the long term, that should also help that nerve stay alive.
We know as we all get older we lose nerves, that’s what happens when we get older, but in MS that happens quicker. We hope that if we can put the myelin back, that speeding up of the loss of nerves will go back to the normal rate.
EK SC, That would be amazing.
AW There have been three very small human trials to improve re-myelination to see if this works. Those trials have been a bit small, there’s been some small effect when you measure how fast electricity travels. It’s a little bit early to be really, really, sure but we’re hopeful.
EK That’s brilliant. But what actually is a stem cell?
AW I think that’s a really good question actually because people often come and say “I want stem cells doctor, give me stem cells!” and you think, well which ones? Because actually all a stem cell is, is a cell that will divide to form another cell and then divide to form a cell which then matures into a cell of a tissue.
AW The ultimate stem cell is an embryonic stem cell. So this is when you get your egg and your sperm and they come together to form the first cell of a baby. That’s the ultimate stem cell because that divides into two cells then four cells etc. Then all of those cells will form all of the tissues of the baby, the skin, the eyes, the brain whatever .
EK That’s extraordinary!
AW It is extraordinary!
EK How do they know how to do that?
AW Well I think it’s extraordinary every time a baby is born, I’m amazed.
SC It’s a bit of a miracle.
AW It is a miracle! However that is what a stem cell is. It’s a cell that can divide into another cell and then divide into something that becomes a mature cell for a tissue. When we talk about stem cells we’re a bit lazy, we just say stem cells, but what need to do is to divide them into what sort of stem cells.
AW So we were talking about Oligodendrocyte precursor cells, these are the ones that go off and form myelin. Maybe you could call them brain stem cells.. or neural stem cells because all they will do is form parts of the brain. As (for example) in your skin, you have skin stem cells that allow you to continuously make more skin.
So in the context of MS it would be wonderful to be using brain stem cells to regrow parts of the brain or to regrow myelin.
But then you’ve got all the other types of stem cells that MS patients know about. These are the ones that are blood stem cells.
So blood stem cells can only have effect on blood. What people are trying to do is to reset the immune system by basically getting rid of the white blood cells that are the immune system in your blood and growing them up again from blood stem cells. These will be blood stem cells to affect the inflammatory end of the disease.
EK Do they think then that cells have become rogue and wrongly attack …
AW Yes. What we think is that the immune cells – the white blood cells what they do is recognise what is foreign, like a bacteria or a virus and what is you. They’re designed to do that, to get rid of things that are foreign and to not get rid of things that are you.
What we think in MS is that this control has gone a bit wrong so that these cells think that for example your myelin or parts of your brain are actually foreign and they start attacking it. This is what we call an auto-immune disease.
AW In the context of MS we think that white blood cells are recognizing you as foreign and therefore damaging you. So the idea of stem cells is if you wipe out your immune system and reconstitute it from your own stem cells then you might hope that those new white blood cells will not think that your brain is something that they should damage.
EK So it’s like a double-pronged attack. You’re dealing with the immune system in the blood cells and the stem cells in the brain to cause re-myelination.
AW I think that’s fair. I think if you think of MS as a two-phased disease. So with early MS where you’ve got immune cells that are going in to damage the brain, that’s where all of the drugs work at the moment. They all affect the immune system. They damp it down so it doesn’t do that.
The side of the research I’m working on is more on the later stages of MS where we’re trying to repair the damage that the early phases have caused.
EK That would be amazing because my friend Al was diagnosed with primary progressive MS in 1993, and there was absolutely nothing that could be done, and Sophie, when were you diagnosed, SC 14 months ago….
SC When you say the brain, my brain’s clear but I’ve got it in my spine. So..
AW, The brain and spinal chord yes, they’re together.
SC I was taken to a meeting in Harley St. – and this is a question I wanted to put to you, about stem cells, – with people saying they could take stem cells from my
fat tissue..
AW So you’ve got your blood stem cells which if you can alter those you might change your immune system.
SC Yes.
AW: You’ve got your brain stem cells that you might harness for repair.
Then you’ve got these fat stem cells called mesokine stem cells.
You get them from the fat and your bone marrow. These are slightly different stem cells in that they don’t make anything particularly useful in terms of they don’t convert into brain cells, they don’t convert into white blood cells.
What they do seem to do is carry a package of goodies around with them that are useful for repair. So it’s like for example of having a bag of good things. They can
travel around, finding areas of damage and then release those good things for repair.
SC Is that, just quickly, do you think that taking these from fat or the bone marrow is about the same.
AW I don’t think it makes any difference.
SC Really, that’s very interesting, thank you for that.
EK I think what’s interesting about it is that treatment is available that wasn’t even thought of 20 or 30 years ago, so people who are facing a really shocking diagnosis have now got hope.
AW I started in neurology about 25 years ago and we had very little in the way of treatment, we had beta interferons, which were reasonable because we didn’t have anything else and these effect the immune end of the MS process. Since then we’ve got many more drugs that can be used and they all were affecting the immune side of it. So many of them are a lot better, many of them are now tablets rather than the injection, which has got to be a step forward. And more are coming out all the time. Even when I started as a consultant, ten years ago, what we have been able to use, the choice has gone up hugely. And so I think that’s a very hopeful place, it’s also a very exciting place.
AW It does create it’s own difficulties because patients have choice and doctors have choice and we then you have to decide which one is the best one for you.
EK/SC And how can you do that, because everyone’s immune system is different.
AW: Well that’s right. If people are on the milder end of MS then you might want to take something with less effect. Less effect comes with less side effects. More effect comes with more side effects. That’s life. You don’t really get something for nothing.
So people often try and treat people at the mild end of the disease with something that works well but doesn’t have too much in the way of side effects and see how people get on with that and then if they do really well, fine, then they’ve chosen well.
If they don’t do so well, then you can move up the hierarchy. That’s one way of doing it and a lot of people will do that. The other way you can say, if someone looks like they have lots of relapses happening very quickly then you might want to go straight up to the top one and really try and control things by using one of the more hard hitting and very effective drugs. Because you are willing to take that risk.
AW Nothing comes for nothing. So whatever the benefit is, there’s a risk. But if you can convince yourself that the benefit is much more than the risk, then it’s worth it.
EK I’ve heard about people who are going to Mexico for stem cell treatment and also to Jerusalem, so I wonder, what is it that they are offering there, that may not be being offered here and is that a different kind of therapy –
And what about people who can’t afford to go to Mexico or Jerusalem?
AW The therapies that they’re offering in these places are called autonogous, innerpoetic stem cell treatment. All that means is that – we were talking about the immune system and the idea is that you get rid of your own immune system, at least partially and then rebuild it from your own stem cells. So what happens is you take some of the stem cells out of your bone marrow, stick it in the freezer, or out of your blood stream, stick it in the freezer. Then you give the person chemotherapy to kill off a lot, perhaps most of the person’s immune system. You then rescue them again by putting their own stem cells back which then can reconstitute their immune system. Clearly you need your immune system otherwise you will die of infection.
SC Is that on a par with Lamtrada, in that it cuts..
AW It’s similar but slightly different. Lamtrada or Aletuzumutab is an infusion of an antibody that kills off quite a lot of your white blood cells and they reconstitute. It’s concept is similar. Actually we don’t know if doing the stem cell transplant is any better than what’s being offered, for example, by taking Alezumutab. We don’t know that.
AW So at the moment when we talk about doing stem cell transplant, it’s a blood stem cell transplant. It’s available in the UK and it’s available on the NHS. But at the moment what we’re doing is reserving it for people with extremely aggressive MS who have failed to respond to the drug therapy.
Now the reason for that is purely the safety side of things.
AW. People in two centres in the UK in Sheffield and London have been involved in a big trial of this which is great because you get all the data back and you can use the data to try and work out what’s going on, and it looks very promising for helping people with the relapsing remitting disease, to stabilise. What we don’t know is what’s going to happen, five years time, ten years time, 40 years time. That’s the big gamble. At the moment you have to fulfill the criteria for it.
AW Now what’s happening is that MS patients are going off to centres abroad and having this done. To be honest that makes me feel extremely uncomfortable.
1. We don’t really know what’s going on in those clinics: they’re not accredited with the world accreditation for health. This is a dangerous thing to do, to take out somebody’s immune system who are therefore going to be exposed to all sorts of infections that might kill them and in fact does, sometimes. So we don’t know exactly what’s going on.
Quite a lot of people who are going are in what we call the progressive end of MS where we know that the immune system drugs don’t work. Therefore why would changing your immune system work in those people. The trial data shows that the stem cell transplants only seem to work in the relapsing remitting people.
Always what happens is that people get more disabled and at the moment there’s less drugs that they can use. They get more vulnerable and more desperate, and then I think perhaps get taken on a ride slightly. So they spend a lot of money for something that may well not help them. I can’t advocate that. I think for relapsing remitting MS people with aggressive disease I think it does work. I think within the next 5 to ten years we might have some idea of how safe it is and also how it compares with other drugs such as aletuzumab.
AW Well that’s a very good question. In the past this isn’t particularly new, it’s the sort of thing people use for blood leukaemias, but also certain countries did this for MS forty years ago. But instead of giving your own stem cells back they gave somebody else’s who didn’t have MS.
But then of course getting something from somebody else is like having a kidney transplant. You then need drugs to try and stop rejecting that. So there’s a level of danger further up – will it work, we don’t know. But you’re right what we’re doing is giving you back your own. Now it may be that those cells have been reset and they’re never going to produce white cells that will attack your brain and spinal cord again. Or it may be that they might. But they might do it in fifty years time, by which point most people will say that’s fine. But they might do it in five or ten years time, we just don’t know that yet.
That’s why we need to do follow up people within trials within accredited centres. I actually think we should follow up the people who go off and do it on their own to get as much data as possible to see whether this is something which is worth the risk. And it might be. But we don’t know that yet.
AW Nowadays with a new diagnosis of relapsing remitting MS there’s a lot of different treatments we can use to damp down relapses and that sort of thing. So that’s good. There are new ones coming up all the time, so that’s good, it’s a happy place to be. The more advanced end of MS, having MS for longer, we’re less good at, but we’re starting to make progress.
EK And so this the blood stem cell side of things that’s different to the brain stem cell side of things that you’re researching. And so how far away are we from this being tested in clinical trials?
AW What we’re trying to do is improve re-myelination. The first trials for that started a couple of years ago, where they were giving substances to make these oligodendrocyte precursor cells, the stem cells in your brain mature into cells that can make myelin quicker. So it speeds up how they go from their stem cells to the myelin forming cell. And there’s been a variety, two or three different medications that have been tested in humans which is good. What they’ve been measuring, it’s actually quite difficult to measure re-myelination without taking the brain out and cutting it out. We can look on scans but scans are just looking at water effectively. And we can do it by working with what they call surrogate markers, which are things that make us thing it’s re-myelinating, but it’s actually quite a difficult trial to do.
AW What they’ve found is that is people given these therapies to improve re-myelination then some of the electric measures, for example how fast things get from the front of the eye to the back of the head, if that improves it suggests remyelination.
I think now having learnt from those trials we think repair takes quite a long time to happen. We’d probably look at the dose, try a higher dose and probably try and get it into people earlier, because if we wait until something’s not working permanently, say a leg that doesn’t work permanently, then maybe the nerves have already died and there’s nothing to re-myelinate.
EK Do they disappear then when they’ve died?
AW Yes. They sort of melt, they get gobbled up by the scavengers of the brain that get rid of dead cells.
EK. Right. Would the stem cell therapy re-generate the nerve cells?
AW That’s a step further. What we’re doing is making the myelin go back on, to put the protective covering back on the nerves. The idea of that is that then those nerves will conduct electricity better, which is what they’ve been measuring. It speeds up the conduction of electricity. But then it also keeps those nerves alive.
That’s the first thing. I think we’ll be able to do that at some point not too far in
the future in humans.
AW If you lose the cells and then want to be able to regrow nerves, think a step further. We need to do one thing at a time. I like to think of it, as when you look on the corner of a street sometimes you get a telephone man who opens that door. You’ve got all that tangle of wires in there and you walk past and you think “I wonder how he knows which wire to use.” Think of that as the brain but on a more huge scale. If you’ve lost that nerve there, we can make a nerve in a dish, and inject it in, I presume. But how would it then know how to join up the relevant bits? How would you get it to be in the right place? How would you get it if you want it to be an arm nerve, ‘move arm’ to then pass the electricity down to move your arm? The ability to get this wrong is quite huge. You could join up the wrong bits. You could not join up anything at all, it could just be a nerve sitting on it’s own. If you increase the number of nerves in your brain, perhaps they’d get over excited and you’d end up with something like epilepsy, where you’ve got more activity. So that’s way over there in terms of where we go.
And also perhaps what we’d like to do is prevent them from dying in the first place. (SC yes.)
I don’t know. I think it depends on the drugs. We’ve had the first trials over the last couple of years, which have been very exciting. There’s not been miracle cures, whatever that is, but they have made a start in getting re-myelination therapies into people. It’s a really good start. We then have to make sure we’re getting them to the right people, that we’re measuring the right things, to see if it works or not. It will take time to get the trials designed better with better drugs, over a long period of time. We’re not talking next year.
EK OK, are these pill based therapies?
AW The ones that have been tried have been both. One has been an infusion, one has been a tablet. But to be honest, if something works, patients will take it, whether it’s an infusion an injection or a tablet. I think that’s less of a worry for me. I want something that works effectively that you can measure over time that makes a difference to patients. You know what I think we will get there. I don’t know when.
EK, You just mentioned about the right sort of people. I’m a bit worried I might not be the right sort of person..
SC Yes. We’re in the line waiting.. Are we the right sort of people?
AW Well we don’t know yet.
EK I assume you’re looking for people who haven’t yet lost all their nerves.
AW. Yes as I said, we clearly can’t re-myelinate something that’s not there. That’s basic phenomenon. So we need to get people whose nerves are still there, but need myelin repaired, exactly so we can put it back again. And I think we need to be fairly selective first in the trials to pick out the people who would really benefit the most, and then we’ll see an effect. Then once we’ve got that then we can start rolling it out to more people.
EK Can I just say about the right sort of people thing, that I’ve been on this drug that has put all my t-cells apparently in my lymph nodes and according to my last scan a lesion that was there is now no longer, and I’ve been told possibly that this means I am re-myelinating. But I still have all the same symptoms. So do I just wait and see if that will start making my nerves…
AW Well anything that goes away is good. That means you’ve repaired something. The question is have you repaired the one that was causing your symptoms. We know that MS lesions can occur in all different parts of the brain and some of them will repair and some won’t. But any repair is good.
EK Yes. We’ll give you our emails and stuff, for when you’re offering your next trial!
Anna presumably the work that you’re doing it’s focused on people with MS, but the treatment will have repercussions across the board, for the treatment of any illness.
AW I think that’s true, if we can improve re-myelination in MS this might be useful for other neurodegenerative diseases, particularly something like spinal cord injury when re-myelinating some of the fibres that are still there might improve symptoms, so yes.
37.17. SC. Thank you for all the work you’re doing. EK Yes thank you.
38.55. EK Anna, thank you very much for seeing us, it’s been such a fascinating conversation – and also for all the amazing work that you do.
SC Yes, thank you We appreciate it, greatly.
ENDS
The Story of Fingolimod
The first ever pill based treatment for relapsing remitting MS.
Vas Narasimhan and Pascale Burtin.
Transcription of interview with Elizabeth Kinder.
We were lucky enough to interview Novartis CEO Dr. Vas Narasimhan for the film, when he was Global Head of Drug Development at the company – And to meet with Pascale Burtin, who is now Head of Strategy & Global Program Management, Development at Novartis Pharma AG.
Pascale is the researcher who really pushed for the human clinical trial of fingolimod that I participated in for ten years from its beginning in 2007. Fingolimod changed the face of MS therapy. It was rolled out onto the NHS as Gilenya, the first ever pill based treatment for relapsing remitting MS.
CLICK HERE for an excerpt from the transcription of our meeting.
MS:OK LIVING LIFE WITH MS TODAY
We aim to offer hope and support to anyone at any stage with MS
MS:OK is inspired by my wonderful MS nurse Caroline D’arcy who reminds me “You’ve got one life, Elizabeth. Live it!”