Presentation Slides with Questions & Answers, 5th UCLP MS Research Day 06-2014
1. Dr Jeremy Chataway and Dr Hayley Moroney: Diet in MS.
2. Professor David Miller: Brand new treatments in MS – what’s here and what’s nearly here.
3. Professor David Baker: What’s new in the lab.
4. MS Nurse Team: How can MS Nurses be of help?
5. Dr Jalesh Panicker: Waterworks in MS.
6. Dr Ben Turner: Progression.
7. Professor Gavin Giovannoni: Why haven’t we cured MS yet?
8. Susan Hourihan: Fatigue-do something!
9. Claudia Wheeler-Kingshott: Demyelination and remyelination in MS.
10. Professor Kenneth Smith: What’s New In The Lab 2? Understanding the causes of MS symptoms.
1. Dr Jeremy Chataway and Dr Hayley Moroney:
1. What kind of research has been done in the relationship between mitochondrial function and MS? Is there any relationship?
If there is a relationship, what about the diet that supports
mitochondrial function, such as diet high in proteins, vitamins,
As far I know there is no evidence in the relationship between mitochondrial function and MS. There were few groups that looked at the fundamental sides of the mitochondrial function, such as oxygenation, or that it may be something wrong with mitochondria. It will be discussed in the afternoon today. In terms of the diet and mitochondrial disease, is it important to have a well-balanced diet. Some people do benefit from certain protein supplements, which normally the neurologists would recommend. But we routinely wouldn’t recommend any additional supplements.
cut beans and peas out of my diet and generally feel better. Then if I
have them again by accident, my tremors increase and I have a cold chill
going down my arm.
There is no data in the relationship between tremors, beans and peas. However if you do feel better without them in your diet, you can avoid and still have a well-balanced diet if you have other vegetables and protein sources. So you will need more fibre and protein from other sources if you are cutting beans and peas.
am now thoroughly confused about Vitamin D. MS nurses prescribe Vitamin
D in high doses, when you said that it is still a very grey area?
It is a very confessing area. Vitamin D is important in epidemiology of MS. However if it is an interventional drug it is still unknown and working progress. I do know of a study in which patients were supplemented with 10.000 international units for up to 6 months and it didn’t show any adverse effects. There are more studies and trials ongoing. In terms of the actual dose, it is again quite difficult, 4000-5000 is safe, 10000 is also probably safe, but that would probably be the recommendations. If you are going to use Vitamin D supplements, it is better to use a good dose, and the chance of toxicity is quite low.
Eliminating food groups. There is a lot of
research showing that gut health regulates the immune system quite
substantially. Do you think it is worth testing people individually for
intolerance to certain food groups rather than just eliminating the
whole food group?
An individual person will have individual problems and intolerance. In terms of the intolerance testing, the gold standard is if you feel that you are intolerant then to just exclude the food for about 4 weeks and see if there is an effect. Later reintroduce the same food and see if the symptoms will come back. It’s a gold standard for food intolerance and everything is very individual. If you are concerned about restricting a specific food group, then I would suggest have one-to-one with a dietician and he or she will be able to look at the whole food intake, your weight and everything else, and your past medical history as well.
2. Professor David Miller:
Why the drugs do not have any benefits for Primary Progressive MS?
You are quite right. Some of these drugs have been tested in Progressive MS, i.e. Betaseron, Copaxone, and we needed those trials. There is a trial on Fingolimod which is about to finish a 3 year trial - and the results will be known later this year. There is also a Natalizumab trial in secondary progressive MS which is on the way and the results will be known in another year or so. So it hasn’t be proven yet that these more potent treatments are not effective in progressive MS, they might yet be, we have to wait for these trials. The reason that you cannot rely on the effective treatments for relapsing MS in progressive MS is that it seems to have a fundamentally different mechanism. In relapsing MS, the process closely relates to immune-system lymphocytes causing targeted damage in the brain but it seems in progressive MS this is no longer primary mechanism. There is rather more diffuse inflammation within the brain itself, which involves different cells, resident cells called microglia, which become inflamed and this causes an ongoing damage to the nerve cells. It is something different and we need to understand it more. I shouldn’t say too much as there will be more talks about it as the day goes by.
Why the white blood cells are attacking our brains? Why does it happen?
It is a very good question actually. I have no idea really. I suppose you could put it in another way - what is the cause of MS? The point of the damage seems that the immune cells are coming and doing that. The question is of course, what makes them do that. Autoimmune diseases are common in our society, they maybe more common than they were years ago, it’s a phenomenon of the modern world, the way our bodies interact with the changing environment, and of course the immune system, which is normally very disciplined and organised and only fights foreign material, foreign antigens, for some reason gets a bit upset and starts attacking our own tissues, like it might be diabetes in pancreas, rheumatoid arthritis in joints, psoriasis in the skin and in MS it is the myelin. There seems to be some susceptibly factors for that, such as certain genetic factors, about 100-150 genes are linked to MS, they are weak associations but they are nearly all linked with control of the immune system. There are also some environmental triggers, which probably again are modulating the immune system, such as viral infections and low Vitamin D levels. There is however a still big gap in our knowledge – what causes MS!
Why would we change from Tysabri to Fingolimod? What are the treatments and chances of having PML and surviving it?
In general this comes up when people who are JC positive and who have been on Tysabri for more than 2 years and then it’s deciding, and it’s a very individual decision, whether to live with the risk and it is still only one in 150-200. PML is a very serious condition if it occurs as there is no treatment for it. It has a 20% mortality. In my experience some people will want to stay on Tysabri because their MS has just changed for the better completely and I understand and support that but then sometimes people feel really concerned too and there is this option to switch. We are still in the phase of getting experience of actually the safety and risk of switching but it does seem – there are quite a lot of new reports coming out – that if it is done within about a 2 month gap in between stopping one and starting the other, it seems for most people to work pretty well.
3. Professor David Baker:
lot or most of the people that on MS drugs already, if you add in
another drug, do you have to look at the safety right from the start
again because you have a combination now of 2 drugs, for example?
We don’t have to go all the way round the board again. When you are doing testing you may do it on top of the drugs, so you will get that safety information. Because drugs do interact with each other, it is a part of development process to make sure that the drugs are safe. If you think about it, as in many other diseases, at the early stages it’s like a straight disease modifying drug and maybe few symptomatics, but as time goes by the drugs will be layered on top of each other, I think.
Do you have any thoughts on statins and blood lipid levels, bad vs good cholesterol?
The question with statins is knowing exactly how the drug works. We did some work with statins ourselves and thought that maybe the action has nothing to do with cholesterol synthesis; it’s just that one of the precursors that creates cholesterol was involved in the process of getting cells into the brain, and if you interfere with that process, cells cannot get into the brain. I think with the progressive trial there is another mechanism as well. If you look for example at Alzheimer’s disease genetics, there is a link perhaps with cholesterol synthesis, immune function and few other things. I think we have to learn a lot more about what statins are and what are they doing. ‘I do not know’ is the answer.
If a lot of your research is trying to get through the fat layer, brain barrier, why can’t you then go straight into the brain?
It is a bit drastic. Baclofen is a good example, you pump it into the spinal cord, but it’s a very expensive procedure and we cannot just keep injecting into the spine. The point that I am trying to get across is that we can use these properties in order to make drugs have a better side effect profile. By just getting the drugs in and then seeing how they work, and once we see they do work, we can try to make them better.
is the chance of the whole drug development thing being quicker than
10-15 years, in the future? Is there any hope for that, because it’s
quite a long time?
How would I speed it up? I would get the regulators to make it less of a tedious process. For example, why do we need to have 3 trials for some drugs? If we can make do with one trial for progressive MS for example, this will make it quicker and cheaper. This is one way, and then in terms of how we do the first bit? Well obviously we need to use science to speed this process up, and it can be done. Some of the companies, once they have an idea, they push these things along really quickly, as they can do them at the same time. When we did it we had to do one step, then wait to get some money, go to the next step and wait again to get some more money. With pharmaceutical companies, time is very important, so they do all of the steps simultaneously. It also depends on what the target is. So for our symptomatic drug we have planned our trial to get done within a month, when it is for neuroprotective drugs we don’t really know how long trials need to bee, maybe a year or if we are to do a proper trial it can be 3-4 years, we don’t know.
What is your blog address?
4. MS Nurse Team:
On behalf of my brother, big thank you to Freya from Royal Free and all the MS nurses, providing an extremely amazing support every day and being there throughout everything.
month MS Trust newsletter mentioned that the average ratio of patients
to a nurse should be 500/1. However it is currently approaching - 800/1.
In Ealing, which is the biggest borough in London with MS patients, the
ratio is up to nearly 1000/1 and it is getting worse. The relationship
and ratio between nurses and patients in the NHNN is great, but I do not
think it is reflected on the country at all.
MS Trust has done an awful lot of work doing research on numbers and looking at the caseloads. I think it is going to be an ongoing challenge. A lot of it will be on developing the services but also on having the support to develop the services. It is a common goal for community or hospital nurses to be able to help you to manage MS as well as possible.
Are the MS nurses have been or will be affected by the governmental cuts?
Yes, we are affected by the government cuts. It is always difficult to balance and also know how much government will give us. The MS trust has recently done a research to see how many patients we should have per nurse and they also have done a bit of work on the impact that we have on you. Hopefully we will be able to use this evidence to show the government how essential MS nurses are to these services. The new NICE guideline that comes out in October and the draft guideline definitely mentions how important MS nurse are for the team. We have to hope it will be a positive move forward. We always rely on 2 charities and they are our most avid supporters, and they fight really hard to make sure that there are always MS nurses around.
5. Dr Jalesh Panicker:
Why do you use tablets or certain type of tablets when people have cognitive problems?
Blood brain barrier separates brain from the rest of the body. These tablets can cross the blood brain barrier and they can go to different parts of the brain and proteins that are there. This is why these tablets can cause memory problems. Not everyone experiences this problem. However If there is an issue, then we will just use the tablets that do not cross the blood brain barrier such as trospium chloride.
Can you tell us if there is a role for sacral nerve stimulation (SNS) in MS patients?
To tell you about SNS, it’s a treatment involving stimulating one of the sacral nerve roots with a device akin to a pacemaker, which is surgically implanted. It has been shown to help with urinary urgency, frequency and incontinence, as well as with retention. The evidence base for its use in MS is limited though. Though it might be useful in the short term, it’s less clear whether it continues to work when bladder dysfunction worsens with MS progression. This becomes relevant considering that it is an expensive device with costs approaching £8000. Moreover, the commonly used devices are not compatible with MRI, though newer MR-compatible devices are becoming available.
6. Dr Ben Turner:
How can a neurologist see a transition from RRMS to SPMS in a patient if they don’t give you MRI scan?
I cannot predict SPMS from the MRI scan, it’s a clinical diagnosis. It’s often a retrospective question as we look at the patient over the last 6-12 months and realise that the patient has gradually changed, but haven’t had a relapse. Now this raises a very hard point to notice who is entering that progressive phase, and that’s why maybe this work about neuro-filaments may be promising. If we can have a test when we think we are not sure, let’s do lumbar puncture and measure neuro- filaments and that would suggest a patient is entering a progressive phase, than if we have an effective treatment for a progressive phase, we can treat it. We always struggled to do lumbar punctures, if we just find a treatment for a progressive phase, we just probably want to start it quite early on anyway. So don’t worry about not having MRI scan, if you have symptoms and a good communication with your neurologist, then hopefully it will be picked up on that.
If I have RRMS does it guarantee that I will definitely develop SPMS?
The key word in MS is heterogeneity. Reviewing statistics, we would say if you have RRMS at 10-15 years you have 50% chance of converting, 20 years you have 80% chance. There is nothing absolute in biology, but yes overtime you have high likelihood of developing SPMS. It can be very subtle, very gradual, and very variable.
have been put on Tysabri, and on one of your slides it says that you
treat SPMS with it. My neurologist has never termed my MS as SPMS and
never discussed that I have entered SPMS stage even that I asked, is he
doing this preventatively?
Well there is a trial on SPMS for Natalizumab. So we do not know the answer whether it does stop the progression. We had quite few patients on Natalizumab for many years and unfortunately we have seen some patients continue to progress. So like any treatment it is not perfect. Hopefully we can see in the study that it slows it down. I admit neurologists try to avoid the diagnosis of SPMS, because it is not good news and as there is no clear treatment. We don’t know many things, but hopefully with the new treatments we should be more honest and discuss it and be more alert to it.
7. Professor Gavin Giovannoni:
Siblings trial was done by Dr Dobson a while ago, are there any results and where can they be found?
paper is now being looked at by one of the journals. What we did find
that between the healthy people and people with the disease the siblings
are half way between the two. The whole purpose of looking at the
siblings was to see whether we can define an intermediate state,
in people who are at risk of the disease and who don’t get the disease. I
think I can say that we have found an intermediate state but can we
now apply it clinically?. The whole idea was to go to a population and
identify people for prevention trials. Ruth Dobson’s study is not about
causation, it is about prevention. Can we identify high risk people and
then do a prevention study on them? We are at the very beginning of
that phase, so Ruth showed that we can identify these high risk people
and it is now how do we explain this prevention study to a general
If the hypothesis is wrong that you have been
working with that it is autoimmune condition, what does it mean for
everybody here and who currently has a diagnosis of MS, and what does
the future have for us basically?
Well, what it means is we will probably have a different type of therapy. I put on the slides the Epstein-Barr virus, it is a virus that probably has the strongest link to MS with everything. That particular virus lives in B cells. For all the very effective therapies in MS, it is the case that every one of them targets B cells. The only common thing to all of the therapies is B cells. Maybe all of these drugs are indirectly working against the virus. One of the current drugs that is at the late stage development, is a drug called Ocrelizumab. This is a drug that depletes B cells. We may find out how the drug works and it may have no implication for the field in general or we may need to bring new types of drugs targeting viruses. All I am saying is that the autoimmune hypothesis doesn’t have to mean autoimmune disease, it may not be, it may be something else that causes the inflammation. These are all treatment strategies.
saw in statistics recently that in England only 18% people with MS
receive the drug treatment comparing to people in the continental Europe
it is about 30% and in the US it is about 50%. It may of course have a
lot of reasons, but obviously finding cure depends on being treated , so
is there any evidence so far suggesting that we are in Britain doing as
well as other European or American counterparts?
Well, we don’t have the British comparison. At the latest meeting that I have been to, called MS Base Registry, which is run from Australia where they get information from all over the world. It is quite outstanding that in Australia you will do much better than if you live in Europe. The difference between Australia and Europe is that Australian neurologists have access to all the effective therapies very early, and it is clearly driven by those people who got onto the most effective therapies very early. The earlier the better. There is data, it does not compare the UK to most of the Europe, the real comparison, and they are doing it right now, will be between New Zealand and Australia. They are geographically similar. Although New Zealand is probably even more restricted than the UK in terms of access to therapies. I am very sure that MS Base will show that if you are a person with MS in New Zealand you will do much worse than if you are an MS patient in Australia. This is the kind of data we need to convince the funders that we really need to treat the disease a lot more actively than we are currently treating it. There is whole lot of cultural reasons why we are behind the curve in terms of adoption of treatments, but I think we will overcome this with data. The problem is that the initial lot of drugs were not that effective and now we have much more effective therapies and we see much better results. Hopefully with the current guidance coming out, we will have access to the effective therapies much earlier.
8. Susan Hourihan:
Modafinil – far more helpful drug than Amantadine, but it is not in the draft NICE guideline?
We can no longer recommend Modafinil, because the European Medical Agency (EMA) issued a warning about side effects of Modafinil. So, we no longer talk about or prescribe Modafinil as the primary treatment for fatigue in MS as the EMA NICE guidelines it can only be prescribed for narcolepsy, so we cannot prescribe it anymore. However, there are many people who had Modafinil prescribed prior to this guidance, and if they are closely monitored by their GPs and GPs prescribe it, then its ok, but we cannot recommend it any longer.
‘Vivid dreams’ - how it was identified and how significant its effect was?
Vivid dreams really only relate to the side effects of the medication Amantadine. It was discovered within the trials and use of the drug. It’s quite a rare side effect but it can occur. So sometimes people find it difficult to fall asleep or stay asleep. Therefore the recommendation is, if you are taking a 2nd dose, to try and take the drug before 2 o’clock in the afternoon which reduces the impact on sleep later and this seems to limit this side effect.
9. Claudia Wheeler-Kingshott:
No Questions and Answers.
10. Professor Kenneth Smith:
No Questions and Answers.