Voiceover:
Welcome to The Raw Nerve, the official podcast of MS Australia, a conversation space for all things multiple sclerosis. Join us for news and views on the latest research, treatments and advocacy efforts, as well as candid and informative interviews with our community, those living with MS, and their families and carers, together with leading clinicians, researchers, and advocates.
Julia Morahan:
Welcome to a special episode of The Raw Nerve. I’m Julia Morahan.
Today we mark World Brain Day, an annual event observed on July 22nd, aimed at promoting awareness and education for neurological disorders that affect individuals worldwide. World Brain Day 2024 is dedicated to brain health and prevention. The World Federation of Neurology, the WFN, proudly leads this initiative in collaboration among all six WFN regions to advocate for the paramount importance of brain health and preventative measures. Today we will hear about brain health from the CEO of MS Australia, Mr. Rohan Greenland. Rohan is also the chair of the Neurological Alliance Australia. And Georgina Carr, CEO, the Neurological Alliance. We’ll also talk to neurologist and specialist researcher, Professor Tomas Kalincik, who works in the brain health space.
So why is brain health important in MS? We know that getting older affects the brain. From our mid-30s, we all gradually lose nerves, with the consequence that our brains shrink and their functioning gets worse. What protects us from the effects of this aging is something we call reserve or resilience. Brains are very flexible. If one area gets damaged, other areas can work harder to compensate. How well our brains do this relies on the size of our brain in terms of our neurological reserve, and our education and ability to learn, known as our cognitive reserve. So brain health is about what we do to maximize this reserve so that we have the necessary resilience to deal with aging as we get older. This ability to compensate the damage explains why people might have MS for some time before noticing certain symptoms and worsening function.
MS can also reduce both types of reserve. As a result, people with MS can experience the impact of aging earlier. This is not unique to MS, and occurs with many other brain diseases. For example, traumatic brain injury. Rohan, you wear two hats, as CEO of MS Australia, and chair of the Neurological Alliance Australia. Brain health is obviously very important for all of the people you represent, those with MS and those with other neurological conditions. Why is brain health so important?
Rohan Greenland:
Well, there’s somewhere between 6 million and 7 million Australians living with some form of neurological condition. There’s 33,300 people living with multiple sclerosis. But there’s something like 600 different neurological conditions. So it’s a very large number of Australians living with some form of neurological disease. So we know that brain health is critical. We know that preventing neurological disease in the first place is so important, and that’s through primary prevention. So there are things that can be done. For example, some of the risk factors for multiple sclerosis include exposure to tobacco smoke, overweight and obesity in adolescents, and lack of vitamin D are all critically important components of risk factors, behavioral risk factors or environmental risk factors, for getting MS.
So we know that prevention is really important in reducing the number of multiple sclerosis cases in Australia. But once people have a neurological condition, for many people living with a neurological condition, or because secondary prevention or support in improving lifestyle is also important for either delaying progression of disease or improving quality of life. So the whole concept of brain health is so important, not just for multiple sclerosis, but for many of those 600 neurological conditions.
Julia Morahan:
Thanks, Rohan. Tomas and Georgina, I would love to hear your thoughts on brain health, what it is and how important you think it is for MS and other neurological conditions.
Tomas Kalincik:
Brain health is a broad and complex term. And the WHO actually spend a considerable amount of time defining what health as such means. So that comes with a definition of normality, what’s a normal brain, not adversely affected brain looks like, what it should function like? And everyone can implement their own personal position. But I view, from the position of someone who talks to people living with neurological conditions every day, that the characteristic of the brain that people value the most is that it constitutes the instrument and actually part of their own persona that allows them to live life at the best possible quality, given the external circumstances. That it equips them with capacity to enjoy what they enjoy doing, be it hobbies, be it work, and make the maximum of the circumstances. And that definition then can be broken down into the individual aspects of that, that it can be being able to engage in highly challenging intellectual activities or physical activities, enjoying time with family.
Now, what that actually means in real life for a person living with conditions such as multiple sclerosis or other neurological conditions or other conditions of the brain. For example, very important aspect is having enough health in our central nervous system that allows us to control our thoughts, to keep our attention and consciousness on a subject, to be present. Because the question, how we achieve all these attributes and maximize the health of our brains is a very, very complex question, even without neurological conditions. And that’s where there is a very important and very challenging area of research of external factors that influence brain health, whether that be diet, whether that be toxins that are potentially present in the environment, or other detrimental effects of the environment in which we live on our central nervous system.
But not to finish on the negative note, I think an even more important aspect is, because we are of course proactive people and we want to define and change our future, the more important aspect is what we can do given the circumstances. What we can change and what we can implement to maximize the mileage that we get out our brains with a big exercise, or whether there are any particular meaningful interventions that anyone can implement in their life, whether affected by MS or not affected by MS, to maximize their brain health.
Julia Morahan:
Thanks, Tomas. Georgina, your perspective.
Georgina Carr:
Yeah, I mean, Tomas and Rohan have spoken really well about both the complexity of brain health, but also the importance of it. And we certainly recognize all those things. If I reflect on the membership of the alliance in England, there’s a huge variability of thinking, the approach to brain health and how people might think of it. But what unites people is ensuring people have the access to the right information so they make the right decision both about treatment but also about factors such as nutrition and socialization and so on to really maximize their brain health. And everybody’s interested in that, regardless.
And if you think about the impact of neurological conditions more broadly, as Tomas has spoke about, they can impact the way you think, you feel, the way you play, the way you socialize, the way you educate, the way you work. And so, doing all we can to get the brain health message across is something we absolutely share your vision for doing in particular.
Julia Morahan:
Rohan, I know that the NAA has just launched a major advocacy campaign ahead of the federal election in Australia. I’m keen to know what you are advocating for and what you have already achieved for people living with neurological conditions. And also, how will these measures help progress research, support and services for people in the neurological community that at the end of the day will help support brain health?
Rohan Greenland:
Thanks for that. Yes, we’ve just held the first ever neurological summit at Parliament House in Canberra. We really wanted to make sure the voice of people living with neurological conditions is heard. Globally, we now have a World Health Organization, a global action plan for neurological conditions, and that’s just fantastic. And brain health is a critical component of that global action plan. But what we lack in Australia is a national Australian action plan for neurological conditions. And so we’re calling, particularly ahead of the coming federal election, for all the major parties to commit to a national action plan for neurological conditions to sit under the WHO Global Action Plan. And Australia has signed up to that. All members of the World Health Assembly, and there’s something like 196 countries that are members of the World Health Organization, have signed up to this global plan.
So we are really calling under that plan, we want to see brain health as a critical part of that. And I might say that as we talk about brain health, we know that what’s good for the heart is also good for the brain. And so, just to reflect on the fact that in Australia we spend less than 2% of our national healthcare budget on prevention. So that actually is quite outrageous. In fact, it was Kevin Rudd, when he was prime minister, he said that was just crazy, end quote. And at the end of his time as prime minister though, we were still spending less than 2%. And today we’re still spending less than 2% of healthcare budgets on prevention. So brain health needs to be part of the prevention agenda, and Australian governments collectively need to up their investment in the prevention agenda.
On top of that, we’re also calling for additional investment in neurological research. So under the Medical Research Future Fund, successive governments have invested in missions. For example, there’s a cardiovascular mission worth $220 million over 10 years. We want to see a greater investment in neurological research because we know that investment in research is incredibly cost-effective and is driving huge changes in terms of not only preventing disease in the first place, but improving treatments and care and improving quality of life for people living with neurological conditions. So we’re calling for a 10-year commitment under the Medical Research Future Fund for a neurological mission. So there’s some of the key things that we are campaigning for.
One of the other things we’re campaigning for is actually a national neurological data set because, unbelievably, last time I checked it was 2024. We do not have a national data collection for neurological conditions. It’s a staggering gap in our national approach to good quality health data. But the good news is, the federal government has recognized this and has invested some funds to begin work to establish a national neurological dataset. So things are starting to happen. We’ve made some small steps forward, but we’ve still got some big mountains to climb.
Julia Morahan:
Thanks, Rohan. So we have also used the Neurological Summit to launch the Count Us In campaign in the lead up to the next federal election, which really focuses on some of those points that Rohan noted about really getting a better idea of the numbers of people living with neurological conditions and other minimum data requirements across the neurological diseases. The Count Us In campaign video is now available. To view the video, please visit the NAA website. Okay, so Georgina, over to you. Can you tell us about the work of your neurological alliance in England in optimizing brain health? And do you feel that brain health is a linking factor across your broad membership?
Georgina Carr:
Yes, certainly. So as I’ve mentioned, we have quite a broad membership, so there’s more than 90 organizations involved in the Neurological Alliance in England. We’ve been around for about 30 years. We’re celebrating our 30th birthday this year, which is fantastic. And there’s huge breadth and depth and variation across that membership. So we have very large members like the MS Society in the UK, right through to organizations like Ring20, which represents a very rare form of epilepsy and are run by just one volunteer. But what unites them is a shared vision for improved treatment, care and support for everybody living with a neurological condition and the friends of family. And there are absolutely some uniting factors in terms of what people feel needs to change. So improving access to specialists is absolutely critical.
In the UK we have some of the lowest rates of neurologists per capita compared to other countries in Europe. They’re also incredibly varied in terms of where they are situated. So about a third of our neurology workforce is based in the Southeast. A third of our UK population is not based in the Southeast. So there’s real issues in accessing the right support. And access to specialist nursing is woefully poor for many people. So there are thousands of people living with MS, for example, living in areas where an MS nurse has got more than a thousand people on their books. So it is really stretched very, very thinly indeed. So it’s a big problem.
Access to the right information, as we already talked about, which of course lots of our members provide themselves is absolutely critical. So people making informed decisions about their treatment care and support and, importantly, what they can do to optimize their brain health as well, which of course means different things perhaps to different condition areas. But nonetheless, promoting the ideas of appropriate and good exercise to keep up the importance of nutrition and linking that to the brain, as well as some of those treatment options that I mentioned.
But also improving access to mental health support is just incredibly important. So we know though that people aren’t routinely asked, nevermind referred for mental health support or mental wellbeing support in the UK. The last time we asked people affected by neurological conditions about this, we had eight and a half thousand people respond. More than half of people hadn’t been asked about their mental wellbeing in the past three years by a healthcare professional, which is ludicrous when you think about the very well known links and comorbidities between certain mental health conditions, neurological conditions, as well as the complex interplay between brain and mental health more broadly. So we absolutely share a vision for that to change so it improves.
And then finally, like Rohan, we are really interested in improving access to research. So access to clinical trials is often a marker of good care more broadly. But also, it could facilitate the access to the rights and the most innovative interventions. But more importantly, ensuring that we’ve got the infrastructure in place for charitable funders of research to roll out and conduct their research. It’s incredibly important that we’re funding the best research that we can in the UK, and that we’re sharing those insights globally is absolutely critical.
And finally, making sure that we’re building a system that is able to ensure success in research is genuinely translated into quality of life for people affected by neurological conditions. So for example, in MS, that means ensuring access to the right disease modifying therapies, for example, and many other therapies that are coming down the track. That success in research comes to nothing if we don’t have the right information specialists in place.
Julia Morahan:
Thanks, Georgina. An incredibly long list of activities and achievements, as well as a lot more work to be done, and a great insight into your population of people with neurological conditions with your survey to ask them about the levels of care and access as well. So, amazing work. You will no doubt be aware of the World Health Organization’s positional paper on optimizing brain health across the life cause, which is a technical compliment to the recently adopted Intersectional Global Action Plan, the IGAPs, that Rohan mentioned on epilepsy and other neurological disorders. It talks about the five brain health determinants of physical health, healthy environments, safety and security, learning and social connection, and access to quality services. Why do you think these big global reports are so important?
Georgina Carr:
I think they’re incredibly important. I think as a country, though, we’ve been on a bit of a journey with the Intersectional global action plan on epilepsy and other neurological conditions. To put it bluntly, I think awareness of that plan despite the UK being a member state was pretty low when it was first signed up. And I think different countries perhaps have different approaches to their international commitments. But what’s clear now is that they’re being marked on this commitment now. So there’s a monitoring piece of work that the WHO are conducting centrally, which is absolutely getting the ears of ministers and the right civil servants and so on. So the UK is really being tested in its commitments to that plan.
And the plan itself, as well as the technical reports that underpin it are pretty ambitious, to be honest, and do provide a very clear framework to be monitoring countries against. So I’m obviously pleased that the WHO is actually following through on let’s say implementation. Can’t underestimate the importance of that. But more importantly, I’m really pleased that the UK is starting to take notice, and it really does help provide really important policy leaders for improvement. So we welcome these global reports, because they genuinely do matter.
Julia Morahan:
We might expand on that a little bit, Georgina. So you’ve had some success in the UK in convincing politicians and key decision makers, and the media, about the importance of optimizing brain health in the neurological community. Do you feel we are making progress in this area?
Georgina Carr:
Yes, I do think we’re making progress. Because as a community, we’re working together in a more cohesive and collaborative way than we ever have done. So we launched the BackThe1in6 campaign, very similar to the Count Me In campaign that the NAA just launched, which is calling for improvements to treatment care and support for people with neurological conditions. And what we would like to see within that is governments across the UK set up what we’re calling a Neuro Taskforce, which would set out a strategy for improvement against some of the WHO commitments in particular. So looking at things like access to data and data infrastructure, quality of data, access to research, specialist provision, mental health support, and actually support for the voluntary sector as well, which is so important in realizing some of this.
And 19,000 people have supported that call, along with a hundred different organizations. And so we have made progress, certainly making that case for change. We have, however, just had a big change of government in the UK, so we’ve now had a complete landslide in terms of Labour coming in and very much the majority government at the moment. However, during the general election campaign, the health secretary made some important commitments by improving access to neurology services, in particular, that we’re really keen to capitalize on. More broadly than that, the campaign has been very successful in terms of ensuring the continuation of NHS England focus on improving access to services and ensuring that we’ve got national clinical directors in place for different aspects of neuroscience. And not all areas get those. So we have got some momentum behind us, but the key thing now is capitalizing on that with the change of government, which isn’t always an easy task, but we’re keen to do it.
Julia Morahan:
Yeah. And we wish you the best of luck with your big changes in terms of your government, but still making sure that we have the voices of people with neurological conditions heard going forward. Professor Kalincik, since Brain Health: Time Matters in MS Report was first launched in 2015, we have had some nine years of advances in MS research addressing brain health. Would you be able to give us some examples of where brain health research in MS is heading?
Tomas Kalincik:
When I answer this question, I start the answer by saying, we live in exciting times. And I’m really pleased to be able to start again in the same way. The times are really exciting in this, and have been really exciting. I feel that the tempo of discoveries is accelerating in this space, and it is really thanks to the huge commitment of organizations around the world, and their increasing advocacy and awareness about the importance of research of brain conditions in my specific area in neuro-immunology, including multiple sclerosis. So we have, thanks to this increasing momentum, we’ve made it a long way from this approach of one size fits all, based on randomized control trials in the use of immunotherapies where basically the information that the clinicians were able to use to treat, to advise patients how to treat their conditions and prevent deterioration and potentially stimulate some improvement. But this information was very plain and simple, saying this treatment does help prevent relapses or does help prevent worsening or visibility. And that’s where our knowledge ended.
Now we actually might well refine. We have, through research of observational data, analysis of clinical trial data, meta analysis, use of causal inference, we are learning about specific clinical scenarios, such as how to specifically treat a certain type of a relapse on a certain type of a medication, and which medication outperforms other medication in certain scenarios, but not in other scenarios. This allows us to see these more complicated sentences which are to the benefit of the patient, where we’re able to say, “Okay, in your particular instance, you don’t have to change treatment.” But to somebody else, I would be saying, “Absolutely, you have to change your treatment and you should be changing from X to Z.” Because now we are in a position to say we have the evidence to guide these changes.
So really, this granularity based on the clinical phenotypes of the disease and the radiological phenotype of the disease are now really making this into practice. A very good example is now represented when we think about, a measurable aspect of this progress is reflected by what we see at the level of regulators. Where, if you look five years back, all over Europe people had to start treatment with low efficacy therapies, with injectable therapies, wait to have that one or two bad relapses and then move on to the next tier of treatments. Now this is ceasing to be the case, and now in increasing number of countries, people have the access to the treatments as they need, and as they decide in consultations with their clinicians what is the best treatment, best fitted therapy for that particular disease phenotype, and from the perspective of the individual prognosis.
Now these clinical phenotypes, we are now starting to make first steps in learning about how these clinical phenotypes may be underpinned by immunological phenotypes. It was just last year, published early this year, that a group of Heinz Wiendl in Münster have published this very exciting study. It is a geeky but very exciting study that is teaching us about how we can characterize the complexity of the cells in the immune system and their constitutional interactions, and how we can describe them in individuals.
And it turns out that there’s individuals with relapsing-remitting MS and progressive forms of MS on the full spectrum of the disease can fall within these different categories on the immunological spectrum. That where in some of these categories, let’s say certain type of a cell, like a B cell, maybe predominant driver of the pathogenesis of MS. Whereas in somebody else, this can be some other cell or other component of the immune system that is particularly important. So this is a very important initial step. And what I’m hoping to really see is how we learn to translate this, to link this information with the clinical appearance of MS. And ultimately, whether the signal tells us something about how to choose treatment that is tailored for that particular type of immunological impairment or immunological disruption in an individual to maximize the effect in that person.
Some of these lessons that we are learning in MS, they’re now starting to learn these lessons and translate them in other rarer conditions such as log associated disease, NMO, spectrum disease. These are conditions that are traditionally underserved because they are rarer and it’s harder to do research in these populations. But having learned from a more common condition such as MS, there is lots to translate into these smaller conditions, and you do not necessarily have to reinvent the wheel every time. But for example, when we are learning about using the clinical phenotype between therapy, we can use that preexisting knowledge from a model disease such as MS.
And finally, a very exciting, and I think critical discovery is around this mysterious virus, the Epstein-Barr virus over the last three years that we have seen. It’s a tantalizing virus. It’s been troubling us for a long time for all the right reasons, because 99% of the world population have been in contact with that virus. But not 99% of world population develop MS. At the same time, a hundred percent of people who have MS also have been in contact with Epstein-Barr virus, and are positive for it. And from the coincidence of the onset of MS, it’s very close with the time where people first acquired Epstein-Barr virus.
So now the question was how can this virus be so? How can it be critical step in the pathogenesis, but yet most people who have the virus did not develop MS? Now we have learned more, just late last year, presented by Tomas Berger’s team, about a faulty elimination of B cells that are altered by this virus, especially those cells that are targeted against our own myelin and our own neurons that may play a critical role. And this faulty process that is driven by impaired and so-called NK cells, natural killer cells, is intertwined with genetic predisposition, exposure to other pathogens, one of them being CMV, Cytomegalovirus. And this really unravels this complexity of the scenario of these phenomena that we have known and been observing around this. And now these pieces of the puzzle are starting to pull together, we’re starting to see how these different environmental and genetic and viral elements of the pathogenesis of MS are starting to come together. So very exciting times.
Julia Morahan:
Yeah, we’re very fortunate to have so much great momentum but, as you rightly say, built on evidence that has been accumulating for a really long period of time, now kind of translating into actual changes to clinical practice. Which is what we want, to actually make a difference to people living with MS and other neurological conditions, quality of life. So I’m going to ask you the opposite question, Tomas. So we have all this great momentum. But in your opinion, where do you think the gaps in brain health research are? If, for example, the government or a philanthropic foundation made a hugely significant injection of funds into MS research, what would be your top two or three areas that urgently need to be addressed?
Tomas Kalincik:
Call me a notorious optimist. People do that. They probably know why. Because I’m going to list the same topics that I have just mentioned. In other words, I think we are on the right track and I think we’re heading in the right direction, towards some very substantial discoveries. So I think what we need to learn next is understand the complex triggers in the pathogenesis of MS. And building on the example of the EBV, EB virus and its interplay with the immune system and the genes. Now understand how these triggers come together, and what else is missing in that puzzle. And understanding that chain of pathogenic events that eventually leads to a complex disease, such as MS, will provide us with new targets that we can target with therapies.
A very good example is that faulty NK cell, or the natural killer cell, that fails to eliminate the B cell. That cell has been bothering me ever since I’ve read about its stories in September last year. And thinking about how we can replace the function of the cells or fix that cell to eliminate the infected B cells that misbehave in the bodies of those people who develop MS. Would that be enough to stop the development of MS in those who do not have the MS but have predisposition? Or in those who have MS, would that elimination of the cell completely obliterate the further damage and stop MS from continuing to cause harm?
I think I made this clear that I’m a big fan of the immunological work that the Münster group has started. And it’s not only the Münster group, there is a strong group in Philadelphia, and there are other groups who are working on the question of immunological phenotype. And I think this is really what we need to understand in detail, which is very closely related to the point that I’ve just mentioned. There’s this understanding of the pathogenesis of MS. But also understanding of an individual who comes to see their specialist not only as a physical appearance of a person with MS, but understanding the cells, the immune system that is driving all these changes that come with the disease such MS. And I’m hoping that this knowledge will allow us to be become more sophisticated in treating MS and targeting the treatments to the mechanisms that are damaged, rather than to the filament that we can see on the surface, or neurological exam, or on MRI.
And finally, one big category of knowledge that has always been puzzling me is this individual resistance or susceptibility to the damage that comes from the immune attack on the central nervous system. There clearly must be a rule, a deterministic factor that defies whose nervous system is going to be more robust to the damage inflicted by the immune system, and who is going to be more vulnerable to these immune attacks. So to understand what drives this vulnerability, whether it’s genetics, whether it’s something environment that can be modulated, would be very important. Again, personalization that will enable us to explain what currently, in the example of multiple sclerosis, is what gives multiple sclerosis [inaudible 00:35:05] why many people present with varied different symptoms. But these are my slim picks.
Julia Morahan:
Thanks so much, Tomas. So our brains are by far the most complex ordinance in our body, allowing us to sense, feel, think, move, and interact with the world around us. The brain helps us to regulate and influence many of our body’s core functions, including those of the cardiovascular, respiratory, endocrine, and immune system. A multitude of factors can affect our brain health even before we were conceived. As we have heard today, brain health is being considered at the global, national, and local level. Addressing this multitude of factors impacting on our brain health is vitally important to our health and wellbeing and our ability to enjoy life to the fullest, especially important for people living with MS and other neurological conditions. Advances in brain health research are encouraging, as we’ve heard from Tomas, but there is always more to do. Our brain health affects everyone around us. Lack of brain health is often invisible. Let’s work together to make it visible. Special thanks to our panel today for shining a spotlight on brain health on World Brain Day 2024. Thank you.
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