S1E10 Research priorities in MS with Professor Gavin Giovannoni

Geoff Allix  00:00

Support for the Living Well with MS podcast is provided by Overcoming MS, a global charity registered in the United States, United Kingdom and Australia, whose mission is to educate, support and empower people with MS in evidence based lifestyle and medication choices that can improve their health outcomes. Please visit our website at www.overcomingms.org to learn more about our work and hear directly from people around the world, about the positive impact Overcoming MS has made on their lives. Now on to today’s episode. In today’s episode, we’ll be talking about how lifestyle factors affect people with MS and research priorities in the field of MS. Today’s guest is Gavin Giovannoni, world renowned academic neurologist specialising in Multiple Sclerosis, based at Barts and the London School of Medicine and Dentistry, Queen Mary University, London. Gavin’s research is currently focused on the Epstein-Barr Virus as a possible cause Multiple Sclerosis, MS related neurodegeneration, biomarker discovery and validation and MS clinical outcomes. So Dr. Giovannoni, you have a world renowned reputation in neurology, could you share a bit about your background?

 

Gavin Giovannoni  01:18

Yeah, so my surname is Italian. My dad was second generation Italian and my mother was second generation English, both were born in South Africa and I grew up in Johannesburg, studied at the university and actually did my specialisation in neurology there before coming to London in 1993 to do a PhD at the National Hospital of Neurology and Institute of Nurgology at Queen’s Square. I did my research in immunology of MS in the CSF lab at the time, but I also worked for Ian MacDonald while I was there. And why did I get into MS? Well, I suppose you could ask why I got into neurology. I had this decision about doing hematology, I was always very interested in the immune system and I was going to do hematology, but then I think I got exposed to neurology, by a great teacher when I was a medical student who made me want to do neurology clinically. And I think my interest in MS was because it was one of the commonest autoimmune diseases in neurology, I think it kind of ticked the boxes for my interest in the immune system and so when I got an offer to come do research in the UK on MS, I grabbed it and that’s how I ended up doing Multiple Sclerosis. So I’ve been in the field now since ’93.

 

Geoff Allix  02:51

So you’ve seen a lot of changes then?

 

Gavin Giovannoni  02:55

We’ve seen enormous number of changes.

 

Geoff Allix  02:57

My father had MS and that was in the ’90s and yeah, there was not an awful lot offered then.

 

Gavin Giovannoni  03:05

Yes, I mean, I actually started in the field before there were disease modifying treatments. And actually, when I started doing my PhD, that was just when the first interferon trial results came out. You know, we didn’t get treatment in this country for another three or four years, and even then the treatment was very limited. So we only really got therapies into people Multiple Sclerosis, at a system wide level across the country, from around 2000 onwards, to be honest with you. So we have seen the field go from, you know, just being diagnostic, and managing the complications of the disease to seeing the first generation therapies and we are know into a third, and we’ll be going into our fourth generation of treatments. So we’ve seen the field completely transformed.

 

Geoff Allix  04:00

And in what ways have you seen the MS clinical and research objectives shifting over the past decade?

 

Gavin Giovannoni  04:07

So I think in the beginning, I mean, when I started, the disease was always considered autoimmune. In other words, your immune system goes awry, and you attack self and we’ve always thought the target has been myelin, I’m quite skeptical it is myelin. But I actually, over the last two decades seeing alternative hypotheses emerge, I think the fact that MS could still be a viral, could be due to virus, hasn’t gone away and actually the evidence has probably got stronger that it may be viral, particularly in terms of causation. But even going on to the autoimmune hypotheosis, we’ve seen a whole lot of therapies emerge and more evidence showing that these treatments make an enormous difference to people with MS. I think in the beginning our target was basically to reduce the frequency, the number of relapses and potentially the severity of the relapses, but now we’ve gone way beyond that and our treatment target is now to try and render people free of disease activity completely. In other words, not only have them relapse free, but to try and suppress the subclinical, the asymptomatic lesions on MRI’s completely. Some of us are even beginning to think beyond that now, we want to actually prevent the end organ, the brain and spinal cord being damaged by a microscopic disease and so what we are actually beginning to target and actually trying to normalise what we call the brain volume loss, which is accelerated in people Multiple Sclerosis, you want to get that into the normal range. So we’re are really taking MS into the same area that rheumatologists have done with joints and kidney doctors have done with kidneys, we’re trying to get those joints and kidneys into old age, we’re trying to get the brain and spinal cord into old age as normal as possible. So our treatment targets have become very ambitious and much more holistic in the sense we tried to do a lot more than we did, you know, even 10 years ago.

 

Geoff Allix  06:14

And what about re-myelination sort of, that if you’d like healing people who are we’ve already got the damage?

 

Gavin Giovannoni  06:23

So there is trials going on in that there’s been a lot of biology that’s been unpacked, discovered around re-myelination, but my personal opinion is if you treat MS you know, early enough and effectively enough, you won’t need re-myelination throughout this because you prevent the damage from occurring in the first place. In people that already had damaged and they’ve got disabilities and problems, you know, we are beginning to do trials of therapies to promote re-myelination in people with the more advanced disease. And we’ll probably get the results of the first phase three, big phase three study later on this year of a drug called High Dose Biotin, in people with more advanced disease to see if it improves function. So yes, we are going in there, but I think what’s important is not everybody will be responsive to these therapies because not everybody will have areas that are de myelinated. It’ll be a small number of people that will benefit from re-myelination therapies in my opinion. And we’ve seen that in the phase what we call the phase two; the early development, that not everybody responds to these re myelination agents, because not everybody has ongoing demyelination. One thing we do know is if you suppress inflammation and stop people having more lesions, you know, and you prevent further inflammation from occurring re-myelination, recovery occurs spontaneously. So that’s something to point out, is that if you treat this disease effectively with quite effective anti-inflammatory drugs, the brain and spinal cord recover on their own, you don’t need to give therapies for them to recover.

 

Geoff Allix  08:10

Okay. So talking about the OMS approach, which includes medication as one of the pillars, but also, do you see other lifestyle modification as being a part or an increasing role in patient care with MS?

 

Gavin Giovannoni  08:30

Oh, definitely. I mean, I call this the holistic management of MS and we now identify a whole lot of lifestyle factors that have been associated with negative lifestyle factors that make people’s Multiple Sclerosis deteriorate much more rapidly and we’ve also got evidence that positive lifestyle factors improve function. So if you really want to optimise the long term outcome for people with MS, you have to focus on everything and this is why I’m promoting the so called marginal gains philosophy, you probably know about marginal gains?

 

Geoff Allix  09:05

Like the cycling?

 

Gavin Giovannoni  09:07

Yeah. David Brailsford did this thing about, how do you know get the best out of your cycling team, well you’ve actually got to focus on every little detail and improve every little detail. So the problem we have in the NHS is that care often is fragmented. So a lot of the lifestyle stuff is not done by MS teams, you know, in hospital environments, but done by the general practitioners, and even a lot of lifestyle interventions, you know, have to be done, even outside of the healthcare system. A lot of nutrition based advice and nutritional therapies are not considered mainstream medical interventions, they’re done outside of that. So this is why I think people with the disease have to be activated, maybe that’s not the right term, but have to be educated to self manage and take on the lifestyle messages themselves.

 

Geoff Allix  10:08

Yeah, I find it quite interesting. I’ve been to some MS meetings for newly diagnosed people that are quite shocked by the number of people who were not prepared to do anything, actually, they would take the tablet, but they wouldn’t change their lifestyle in any way other than that. They wouldn’t stop smoking, change what they ate, do any exercise. But yeah, I think you do certainly see a difference in the outcomes, having met lots of different people. And actually, one of the factors that we talk about in OMS is a sort of mental side of it. So be stress, reducing stress and mindfulness, but also the positivity, I think, if you’re, I think people who want to get better, it does seem to be just in the fact that you are trying everything and you actively want to get better. It does seem that those people have a better outcome.

 

Gavin Giovannoni  11:07

Yeah, unfortunately, it’s easy to blame people and point fingers at them for not sorting out their lifestyle, but there’s a big body of evidence out there, we refer to them as the Social Determinants of Health and these are factors that play out at a population level and, you know, they got to do with politics and social issues that are not, you know we kind of think they are in the hands of the individual, but they’re not, you know, this relates to inequality, poverty, you know, education attainment and, you know, essentially hope to be honest with you, there’s a lot of people out there who are living in poverty, they haven’t really had the education to understand the importance of lifestyle factors and they really don’t have any hope in the sense that they can’t see anything positive in their lives. Now, you can blame those people at an individual level but I think it’s not their fault, it’s a social issue. The problem we have in the United Kingdom is that there’s so much inequality, it’s such a big difference between people in the top end of society and the bottom end of society and you know, unless we address those issues, it’s going to be hard to get lifestyle interventions adopted across the socio economic spectrum. Just give you an example. I’ve just come back from a meeting in Norway, the European Association Neurology meeting and you know, in those Nordic countries where there is very little inequality, the adoption of lifestyle intervention is much greater than we have in the UK and I suspect it’s because they’ve got the social determinants of health sorted out at population level. So and they do lots of interesting things at a policy level to encourage healthy lifestyles and, you know, it’s difficult for that to happen at a population level in the United Kingdom. But anyway, if people are interested in reading about this, a fantastic book called The Health Gap by Michael Marmot, who is the Professor of Public Health at the London School of Hygiene and Tropical Medicine, at UCL, and he goes through all these issues in detail in his book and it’s quite, it’s quite a profound observation how inequality drives a lot of disparities in health outcomes and MS is no different, MS is just one of the diseases where the the social determinants will have an impact.

 

Geoff Allix  14:09

And in other western illnesses if you like; heart disease, diabetes, and so on, there does seem to be a lot more official guidance in lifestyle in what you eat, the exercise you do, and so on. Certainly like diabetes, obviously, there’s a lot of encouragement, heart disease a lot of encouragement. There doesn’t seem to be that officially for MS or it doesn’t seem to be across the board. My neurologist does run, sort of meetings for newly diagnosed people where he does encourage them to eat sensible diet, do some exercise, reduce stress and these things, but it doesn’t seem to be an official, you know, in this country, the NHS but equally in America or Australia, other countries, it doesn’t seem to an official guidance that they would necessarily have in something like heart disease or diabetes. Why do you think that’s the case and do you think that’s likely to change?

 

Gavin Giovannoni  15:09

Yeah, I think it’s got to do with the evidence base, you know, we are always told to practice evidence based medicine and I think the evidence base in cardiovascular diseases is you know, much firmer than there has have been, you know, population-based studies. The problem with these studies, they don’t prove causation, they just associations. In other words, it’s very difficult to do lifestyle intervention studies in terms of randomisation, you know, you randomise somebody to this lifestyle intervention and somebody to that, because it’s not like giving a drug and placebo, it’s hard to give a lifestyle intervention as a placebo. So a lot of the evidence that is accrued in the cardiovascular diseases, accrued over the last 50-60 years and so they’re much more confident about the link between lifestyle factors and cardiovascular outcomes. Whereas in the MS space, to be honest with you, there isn’t really what we would call class one or even class two evidence about these things. But my personal opinion, is it’s not about that, it’s about general health anyway, you know, we should be promoting general health in anybody with a chronic disease and particularly, as we don’t know that people have Multiple Sclerosis, are much more likely to have so called comorbidities, cardiovascular comorbidities, they’re much more likely to be hypertensive, overweight, dyslipidemia, get diabetes, this has been now well established. And so because of that, we as a neurology community should be promoting all these lifestyle interventions. Because at the end of the day, those lifestyle well, those ‘lifestyle diseases’ have been linked to a poor outcome in MS. So it makes complete sense to target those and try and prevent them from occurring in the first place or if you have them to treat them quite aggressively, to improve outcomes as part of our brain health message. You know, to maximise lifelong brain health in people with Multiple Sclerosis, it’s not just about treating MS, but it’s about treating all those other aspects that will reduce brain health, and obviously making this worse.

 

Geoff Allix  16:17

That’s similar to it, I put it to my neurologist, and quite early on and said, I’m following this diet and lifestyle approach, which equals the Jelinek approach,  George Jelinkek, who sort of found OMS and he said, ‘well, there’s there’s not evidence that that will ever, not currently wouldn’t currently become mainstream. But having said that, if you follow that approach of healthy diet and lifestyle, you’re less likely to get heart disease, diabetes, cancer, numerous other things and it might well improve your MS’. So basically, the thing to consider is don’t spend loads of money on it and then if you’re happy to miss out on, you know, certain foods you might be cutting back on and you’re happy to do the exercise, then all in all, it’s not gonna do any harm and you actually might find it’s actually helped in another area, like heart disease or something.

 

Gavin Giovannoni  18:32

Yeah, I completely agree. I mean, the the George Jelinek the approach is quite, it requires quite a lot of self discipline. And we know that self discipline is rewarding itself, I mean, you know, people who do live with quite a disciplined life, get a reward from it and so, you know, whether it’s the lifestyle intervention or that people definitely feel better when they maintain a healthy lifestyle and stick to it. I kind of agree that in terms of the dietary advice, we don’t really have evidence and I’m not 100% convinced any particular diet is better than another diet in the MS space. I think you just have to live a healthy diet, because the thing about food is, it’s not just about calories and nutrients. It’s also about you know, food and eating plays a really important role in society, you know, we have a lot of traditions and rituals around food. And so you know, your diet has to be congruent with your social situation. You know, I feel that if it’s going to stop you eating and being social with your family and friends, by sticking to a specific diet, that’s not ideal, you really need to keep your social networks going and a lot of social networks are linked to eating, so you need to know your diet has to be congruent with your social situation. I keep telling my patients that there’s no point in going on a strict diet, if it’s going to cause problems in your family, for example. So you need to be quite sensible about diets, about which diets to go on. I think from a scientific perspective, you know, basic science, in terms of brain health, the diets that have been shown in animal models, and in some human studies to actually protect the brain when you’re protective, are calorie restriction, reducing calories to very low level, which is not feasible in MS. I don’t think calorie restriction is ideal because you need calories, and the other ones Intermittent Fasting and the Ketogenic diet. So those two diets probably work in a similar way, they trigger these neuro protective pathways in the brain and your body. I mean, it is now beginning to develop an evidence base, particularly with ketogenic diets in MS, I’ve seen two studies by two different groups, showing that people who are on ketogenic diets for intermittent fasting do better than those who are not. So I think those diets should be actually researched. And one of our therapies in MS, which is called Dimethyl fumarate, or Tecfidera, it stimulates pathways in the cells that are extremely similar to what ketogenic diets trigger, so I suspect there’s an overlap between ketosis and the mode of action of Dimethyl Fumarate.

 

Geoff Allix  21:39

So we want to get into some of the research things as well, which is one of the key reasons I want to speak to you, but just very quickly on that point, with intermittent fasting, because I’m currently doing intermittent fasting on a 16-8 daily, so I don’t eat anything till lunchtime and then don’t eat after eight in the evening. But there’s all these different types, so there’s a 5-2 where you where you don’t have much to eat on two days a week, there’s, you know, 16-8, where you don’t have much to eat over 16 hours on a particular day. Is there any evidence that one of those is better than others? Or some which where they just have literally a water fast for a day? And there’s all these different approaches?

 

Gavin Giovannoni  22:26

No, I think at the moment, we don’t have any evidence. But I think what’s common to all of these is they trigger ketogenic programs, they trigger the biological programs that causes your cells to go into what we call a low carbohydrate state. And, you know, so that what I think what’s common to them is the metabolic pathways that get triggered, and the new protective pathways that get triggered. So I think that’s what’s common to them all.

 

Geoff Allix  22:55

So you’re saying if you find something that fits in with your lifestyle, because that’s why I find this works for me, because I like to still eat with my family, I can eat with my friends that didn’t affect me at all. I just don’t have breakfast really? And have a slightly later to lunch. So I’m used to it, it’s fine.

 

Gavin Giovannoni  23:15

I mean, this is now not in the MS space, so this is just looking at longevity, there’s been lots of studies on populations that live very long and healthy lives and common to those diets is also low calorie, or very basic diets with quite a lot of calorie restriction or intermittent fasting in those populations as well. So outside of MS, there is a lot of circumstantial evidence supporting, you know, intermittent fasting or caloric restriction to extend lifespans. So, you know, I think, I think the biology of caloric restriction, intermittent fasting is, you know, very interesting, and I think it’s highly relevant to MS. Because our current food environment we live in is just, you know, abnormal, we, you know, most people are eating sugar, for example, or processed carbohydrates 24/7, essentially, we have forgotten how to be hungry. And I think if you look at the evolution of man, you know, we didn’t evolve in a food environment where we had calories on tap 24/7. So I actually think from an evolutionary perspective, we need to go back a little bit and just learn lessons about our biology and I think this is relevant to people with MS. It’s, remarkable how many of my patients who, not me recommending it, come to me and say, I’ve been doing the intermittent fasting diet, while I’m doing a low carbohydrate diet, and I feel so much better. There’s so much, you know, I’m beginning to find this in my clinic anecdotally that these people come back and are extremely positive about it. We do need to study it and there are studies going on now both in Europe and United States, particularly North America, looking at these diets, and the outcome in MS.

 

Geoff Allix  25:14

And can I ask, as a specialist on the call, what are some of the most promising research frontiers and where sort of MS research is going, now? What what does the future hold do you think?

 

Gavin Giovannoni  25:29

I think what we’re doing is, we’re moving into combination therapy space. So you know, not just anti-inflammatory. There’s a series of trials now with add on so called neuroprotective therapies, these are drugs to try and slow down the loss of nerve fibers, because we’ve got the add on your remyelination and your restoration trials. Some of us are looking into more advanced disease, these are people that are really have major problems of loss, potentially lower limb function, and we are trying therapies, even wheelchair users to try and protect upper limb function. And so that they can take in the treatments into a stage where we can’t use them at the moment and you’re probably aware that on the NHS, you’re not eligible for any of the disease modifying treatments, if you’ve lost lower limb function or otherwise a wheelchair user, so that’s what we would call next frontiers, more advanced disease. And then there’s a lot of environmental factors that are modifiable in terms of trying to prevent MS and so the MS community is now looking towards doing prevention studies, taking high risk people so these are normally children or siblings, brothers and sisters of people with a disease or with a much higher risk of getting the disease and seeing if we can prevent them from getting MS. And the two main ones there would be Vitamin D supplementation and the other one is trying to prevent infection with the virus; Epstein-Barr Virus, it is so strongly associated with MS. So you know, for me, those are three things are the real excitement, combination therapies, treating more advanced disease to protect upper limb limb function and MS prevention studies.

 

Geoff Allix  27:11

And so that’s sort of prevention and family is one of the pillars of the OMS approach, actually and I’ve got I’ve got two children and I give them Vitamin D supplements. I often look at these sort of what are the potential benefits and what are the risks? And you think, okay, the risks of Vitamin D, because they don’t have much dairy anyway so it’s a limited amount of risk, because I was told, okay, the biggest risks kidney stones, Vitamin D makes you more efficent. Right. So that’s sort of one thing I’m doing so certainly the Vitamin D for my children, but you also mentioned Epstein-Barr Virus, is there, is there something that people can do independent of the research coming out? Is there anything that could be done to try and avoid that?

 

Gavin Giovannoni  27:44

So that’s based on a small study from India from the 1960s on kidney stones, and if anything, it reduces kidney stones. The reason being is when you get very low Vitamin D levels, you produce a hormone called Parathyroid hormone, which mobilises calcium from the skeleton and so, some of that calcium goes out in the urine. So very low Vitamin D levels, actually, you get more calcium in the urine. Soon as you go into Vitamin D supplements and you suppress what they call the Parathyroid hormone response and actually, the calcium levels in your urine go down, not up. So Vitamin D, and most people now in the field, think that original report was not true, biased or false. And there is no evidence that Vitamin D supplements cause kidney stones. Now, if you take Vitamin D in combination with high doses of calcium, that’s a different story. But the cause then is not the Vitamin D, but the calcium. So our recommendations is if you’re going to take Vitamin D supplements, particularly if you are healthy and young, there’s no need to take calcium supplements in parallel. So we don’t advise calcium supplementation. It’s a virus that’s ubiquitous. By the time you’re in your mid 30s, about 95% of the population get infected with the virus, it’s transmitted from saliva because it’s excreted in the saliva. And there’s nothing you can do to avoid being infected with the virus. What may be useful is if people get infected when they’re very young, but we don’t know that what happens is the transmission rates have change, you know, the real risk factor is when you get the virus when you’re much older and when you’re a teenager, adolescent or adult, and you’re getting Infectious Mononucleosis, or Glandular Fever, which is the symptomatic infection from Epstein-Barr, that’s actually quite an important risk factor for MS. But you can’t stop people getting that at the moment. So their idea was Epstein-Barr Virus is actually to do a vaccine study to prevent you getting infected with it. But the vaccine is not ready yet for primetime, they’re under development still and we’re hoping to have a vaccine in about three to four years time that could potentially be put into trials to try and prevent people getting MS.

 

Geoff Allix  30:42

Is there likely to be any more treatments for people with progressive MS, beyond Ocrelizumab which has recently become available. Is there more on the horizon for them?

 

Gavin Giovannoni  30:58

We got this drug in the secondary secondary progressive space called Siponimod. And now that we have got positive trials, and the pharmaceutical industry are going to be doing more and more trials in progressive MS, because I think what we learned from the Ocrelizumab in primary progressive and Siponimod in secondry progressive is that we need to design our trials differently, they need to be obviously bigger, a little bit longer and they need to be event driven. In other words, in the past, we did trials for say two years only, now we let them run openly until people have had enough events. In other words, we know how to do the statistical powering of these studies. So I see a whole lot of other disease modifying treatments emerging for progressive or more advanced disease. And the difference is the treatment effect is going to be lower simply because people have got quite a lot of disability already and so they mustn’t expect the same treatment response rates as they got in the early stages of the disease. Because some of the treatment responses actually recovery of function and these people have lost so many nerve fibers, they won’t get recovery of function.

 

Geoff Allix  32:05

And can I start to wrap this up, what’s the most important advice that you’d give to someone today who’s been newly diagnosed with MS?

 

Gavin Giovannoni  32:16

Get yourself onto a treatment, disease modifying treatment as soon as possible and make sure you get monitored, so your disease is controlled. In other words, if you’re not responding to the particular disease modifying treatment, you need to be on a more effective one. So it’s about being treated to target and also to take all those lifestyle issues very, very seriously. So they should read up about it, I would recommend reading our Brain Health, Time Matters document which is online and that goes through all the important lifestyle issues.

 

Geoff Allix  32:48

And is that on the Barts?

 

Gavin Giovannoni  32:50

No, not a particular website, if you just Google ‘Brain Health Time Matters’ there’s a specific website that you can download that document, but it talks about not smoking, making sure you exercise, get good sleep, making sure you go onto a healthy diet. It does mention a little bit about Vitamin D supplementation, I think that’s critical whether or not that makes any difference once you’ve got MS.  And make sure that you get your comorbidities screened for, make sure you get checked out for hypertension, etc. So it’s basically looking at your life and doing everything you can to make sure you are as well as possible. That’s what I’d recommend. And also don’t don’t put your head in the sand, don’t ignore things. A lot of people with MS go into denial, that’s that’s a normal behavior when you get a chronic diagnosis of chronic disease. But it’s important that once you accept the diagnosis is to read and keep yourself up to speed with what’s happening.

 

Geoff Allix  33:57

Not to just blatantly plug you while you’re on but I think your Twitter feed is an excellent source of information to keep up to date if anyone’s on Twitter.

 

Gavin Giovannoni  34:07

Yeah I mean my personal opinion is if you really want to you find, this is one of the problems other things about the internet there’s a lot of false information out there so try and find yourself a reliable, usually things like MS Society, MS Trust, Shift.MS. You know, these people put out reliable information, but it’s important that you don’t just accept everything you read on the internet as being fact and you question it and do a bit of research around it to make sure it’s reliable information.

 

Geoff Allix  34:39

I’m very skeptical of someone who wants to take my money as well. If theres a financial side of it involved you start thinking I’m a lot more skeptical person.

 

Gavin Giovannoni  34:51

Yeah, so yeah, we didn’t charge anything for information.

 

Geoff Allix  34:55

And just on the medication thing, are you the opinion to hit it hard to hit it early or wait and see approach?

 

Gavin Giovannoni  35:03

I’ll wait and see. In my personal opinion, I don’t like the term hard, I think we just need to hit it early. You know, some people will be responded to drug X other people might will fail that new drug Y. It’s about effective therapies, I’d rather say treat early and effectively and effectively could mean anything from what we call platform second tier or third tier. It’s basically finding out which treatment your responses to. So it’s, it’s more to be about effective.

 

Geoff Allix  35:35

Okay, that’s been very interesting and thank you very much for joining us.  With that, I would like to thank you all for listening to this episode of Living Well with MS. Remember that there is a wealth of information at overcomingms.org including show notes and an archive of all Living Well with MS episodes. Once again, that’s overcomingms.org. There you can also find OMS friendly recipes and exercise tips, connect with other OMSers in your local area through our OMS Circles program, and learn about the latest research going on in the MS world generally and related to OMS specifically. I encourage you to register on the site and stay informed about the latest news and updates. I also encourage you to subscribe to this podcast, so you never miss an episode and please feel free to share it with others who might find it of value. Let us know what you think about the podcast by leaving a review and if you have ideas for future episodes, we’d love to hear from you. So please contact us via our website overcomingms.org. Thanks again for listening, and for joining me on this journey to Overcoming MS and Living Well with Multiple Sclerosis. I’m Geoff Allix and I’ll see you next time.