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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.

Fiona McKay

Hello and welcome to The Raw Nerve. I’m your host, Dr Fiona McKay, Deputy Head of Research at MS Australia. Today, we mark World Brain Day, an annual event observed on July the 22nd, which aims to foster quality neurology and brain health worldwide.

The World Federation of Neurology proudly leads this initiative in collaboration among all six broad geographic regions, to advocate for the paramount importance of brain health and preventive measures.

World Brain Day 2025 is dedicated to ‘Brain Health for All Ages’. Its call to action is, ‘to protect neurological wellbeing from the earliest stages of development through childhood, adulthood and into older age’, and is committed to, ‘care, equity and access for all’.

Today, we will hear about brain health from three MS research experts, Dr Olivia Wills, Dr Steven Petratos, and Dr Izanne Roos, who will tell us about some exciting outcomes from research funded by MS Australia. We’ll discuss how to keep your brain healthy while living with MS, early intervention in MS, treatments and monitoring at different stages of life, and some exciting new research to develop therapies to repair the brain.

The ‘Brain Health for All Ages’ theme helps the World Federation of Neurology draw attention to the unique neurological challenges and opportunities that arise across different stages of life and to encourage a more coordinated global action that is responsive to age and region-specific needs.

The burden of neurological disease is not evenly distributed worldwide, and significant differences exist across age groups and regions. The differences highlight bigger issues, such as unequal access to health services, workforce capacity issues, unequal public health investment, and the impact of social and economic conditions on people’s health. World Brain Day raises awareness of all these issues as they pertain to brain health with the goal of improving equitable access to neurological care.

Having a healthy brain that functions well is important for people with MS. And a bit later, we will talk about some of the key steps that are recommended. So, today on The Raw Nerve, we’re talking about the brain and brain health in MS and ways to look after not only your brain health, but your overall health and wellbeing. And now I’d like to welcome three guests into the studio to speak about brain health, marking World Brain Day 2025.

Firstly, we have Dr Olivia Wills, Associate Lecturer, Associate Research Fellow from the School of Medical, Indigenous and Health Sciences in the Faculty of Science, Medicine and Health at the University of Wollongong. Olivia is also an accredited practicing dietitian. Welcome, Olivia.

Olivia Wills

Thanks Fiona and hello everyone.

Fiona McKay

And from Monash University, we have Dr Steven Petratos, Senior Research Fellow and Laboratory Head of Regenerative Neuroscience and Development Group in the Department of Neuroscience and the School of Translational Medicine. Welcome, Steven.

Steven Petratos

Thanks, Fiona, and I appreciate your invitation to discuss some of our laboratory’s exciting research.

Fiona McKay

Thanks, Steven. And rounding out the panel, we have Dr Izanne Roos from the University of Melbourne and Senior Research Fellow in the Department of Medicine. Izanne is also a neurologist and Deputy Director of the Neuroimmunology Centre and Department of Neurology at Royal Melbourne Hospital. Welcome, Izanne.

Izanne Roos

Hi Fiona, it’s a pleasure to be here with you all today.

Fiona McKay

Thanks, Izanne. We’ll start with you, Olivia. And we’re actually very lucky to have your expertise here today as you’ve recently completed your PhD on brain health in MS. Now, there are many definitions of that term brain health, but could you explain to us exactly what is brain health from your perspective?

Olivia Wills

You’re right, Fiona, there are many different ways that people define or talk about brain health in MS or more broadly speaking as well. Traditionally and especially in the context of MS, brain health has really been spoken about in medical terms. So, one idea that has come up is called neurological reserve. And this means that when MS may damage one part of the brain, other parts can step in and work harder to keep things functioning as normally as possible.

But through my research during my PhD, I spoke to a lot of different people living with MS and healthcare professionals and learnt that brain health is about so much more than just that medical side of things. So, many people I spoke to connected brain health to everyday life, like being able to think clearly, remember things, learn new information, manage emotions, stay productive at work, and even enjoy meaningful relationships.

So, we’ve really started to move away from that narrow medical lens of brain health and now really challenged to think of it in a more holistic way. So, a definition that I developed and tested through my PhD was brain health as the ability of the brain to adapt and compensate to still retain that optimal neurologic function but irrespective of the presence of disease. It recognises the person as a whole being and can be referred to as both a relative and dynamic concept that is influenced by biological, psychological, social, interpersonal and contextual factors.

Fiona McKay

Fantastic. Thank you, Olivia. That’s a lovely definition and really encapsulates the whole of what we’re trying to talk about today. Now, Steve, you’re a researcher in MS neuroscience. Can you tell us very briefly what’s happening in the brain in MS that compromises brain health from a biological perspective?

Steven Petratos

Yeah, thanks, Fiona. Well, of course, MS is caused by the immune system basically mistakenly attacking the cells of the brain, particularly those cells that myelinate the nerve fibres. Of course, myelin is the protective covering of those nerves and not only the brain, but other parts of the brain that are extensions, such as the optic nerves, those nerves that connect the eyes to the brain and the spinal cord, of course. And of course, those three aspects are collectively known as the central nervous system.

So, what happens when relapses occur is when the immune system produces these focused areas of immune damage to the myelin, of course, that coating of those nerve fibres and this can result in a temporary or permanent worsening of the symptoms. And these are shown in time and space, of course. However, a proportion of people with MS experience disease worsening, even when there are no obvious new lesions or relapses.

Now, this type of disease progression in MS is also referred as smouldering MS or we commonly now term it as progression independent of relapse activity. And some of those things that can cause this, although we don’t know why this is really occurring, but we believe that infections could be a cause, lifestyle factors, things like vitamin D levels, smoking, diet, particularly you know, a really good microbiome can help protect this. And lack of exercise. Of course, that sort of culminates with age-related damage to nerve cells and where progression of MS symptoms can be disabling, affecting the quality of life of the individual.

And so, other aspects neurobiologically that have been defined, include the loss of neurons or other supporting cells in the brain, where the brain shrinks through loss of the volume of the brain. Excessively high levels of specific neurotransmitters. These are chemicals that can, in excessive levels, can damage nerve cells and that produces loss of brain’s buffering capacity to cope with excessive, these toxic chemicals and also, failure to repair. So, the compensatory mechanisms that can occur in the brain and of course, research is actively investigating all of these to try and limit MS progression.

Fiona McKay

Thanks so much, Steve. So, there’s a lot going on and a lot we need to address in terms of therapy and at the research level. Now, Izanne, you’re an MS neurologist. Can you tell us a little bit about how the brain copes with this damage and why it’s especially important to focus on brain health for people with MS?

Izanne Roos

The brain has this fantastic capacity to compensate and adjust for damage that occurs. This happens for a number of reasons, and we typically do refer to that as neurological reserve as Olivia mentioned previously. The brain remodels itself to compensate for the loss of nerves, perhaps due to a process called neuroplasticity where it can reroute signals to undamaged areas or perhaps can even adapt undamaged areas to take on new functions.

Now we see this quite acutely if somebody has a stroke and they recover from that. But in MS we see this in a number of ways as well. Sometimes when people present with their first neurological episode, we might do an MRI scan and see that there is damage that’s occurred over time, but people might not have realised that that’s been going on and that’s due to that neurological reserve capacity.

Also, due to the ability to compensate for damage, people might also deteriorate in a delayed onset, where there might be worsening of function as they get older and some of that ability to compensate for previous damage might reduce. And that really does bring us back to the idea of brain health, because as we age, there is some shrinking of the brain that happens naturally over time but that might be particularly accelerated in people with MS, and in fact can even occur at the earliest stages of MS. And for that reason, it’s important that we focus on these other aspects of brain health which also compensate to brain reserve, so we can really maximise people’s function not just from an MS perspective but also from a whole health perspective.

Fiona McKay

Thank you so much, Izanne. So, moving now to Olivia, your research really focused on developing recommendations for people living with MS to maximise their brain health. Can you tell us a little bit about what prompted that research and what were the recommendations that you came up with?

Olivia Wills

The spark of my PhD really began back in 2016 around the time of the MS Brain Health Initiative led by Gavin Giovannoni, which first really highlighted the importance of a timely and accurate diagnosis in MS, and secondly, starting a high efficacy disease modifying therapy quite quickly.

So that initial work was really, of course, inspiring, but quite medically focused, with not much discussion about what can people living with MS be doing themselves to be living well with MS. So, as I started talking to people with MS and a range of Australian healthcare professionals, I noticed people living with MS knew what they could be doing with regards to self-managing their disease, but many really struggled to actually make and maintain those changes over time.

And we found that speaking to professionals, clinics were often short on time and limited in their consult duration. And there were not always enough follow-up support through these centres as well. So, it became really quite clear that knowing the advice enough wasn’t enough for people to put that into practice and translate that into real life.

So, in 2023, with the support of a scholarship from MS Australia, I led a study to build a more complete and practical approach to brain health for MS. So, during this research, I interviewed a range of different people living with MS of all different backgrounds and walks of life, a range of healthcare professionals, including neurologists and GPs and allied health professionals, researchers and academics and national advocates across Australia as well.

Together, we were able to develop 16 consensus-based lifestyle recommendations to maximise lifelong brain health for people living with MS. And for clinicians, these were paired with key behaviour-change strategies, to really support that translation into a real-world setting.

So, some of these key lifestyle recommendations, which are for people living with MS across all age categories, include things like regular physical activity and exercise, eating a balanced diet, maintaining a healthy body weight, avoiding smoking, both passive and active, and limiting alcohol intake. Prioritising good sleep habits and sleep hygiene fits into that conversation as well. Looking after good mental health and what’s even more of topical interest now is gut health and maintaining and how to improve gut health. Staying socially and cognitively active, ensuring sufficient vitamin D levels, managing other health conditions. So, things like diabetes or high cholesterol or high blood pressure, and importantly, starting a disease modifying therapy early and maintaining good medical compliance.

Fiona McKay

Wow, that’s a great list. And most of those, I think, you know, are really applicable to all of us, aren’t they? But even more important when you’re dealing with a chronic disease. So, Olivia, is there good evidence for the benefits of maintaining brain health in MS in this way?

Olivia Wills

We’re definitely learning more and more. One of the biggest challenges that we face is that brain health is still quite subjective. So, it can be measured in a lot of different ways. So, things like memory, thinking skills, emotional wellbeing, and quite traditionally MRI brain scans. So, it is quite tricky to capture it all in one clear measure. But what’s really exciting is that research is increasingly focusing on brain health in MS.

So, in the past, we really looked at physical disability or relapse rate as an outcome through research. But now there’s much more attention on yes, how the brain is functioning overall, but how are people feeling day-to-day living with MS as well. So, studies are showing that looking after your brain through things like I mentioned earlier can make a real difference.

We do have strong evidence that this may reduce the number of MS relapses and disease severity, improve thinking and memory, and even improve mood and overall quality of life. So, it’s still a growing area of research, but what we do know already is that taking care of your brain doesn’t just help manage MS, it helps someone feel and function at their best across all ages, no matter where they are in their journey of MS.

Fiona McKay

And that’s so important isn’t it and it really gives the person with MS some power, doesn’t it, to really have something they can modify in their life and gives back some control.

Olivia Wills

Absolutely.

Fiona McKay

So, one of those recommendations you mentioned is to maintain a healthy diet and because you’re a dietitian I can’t not ask you this question. Do you have any general recommendations for diet for people with MS?

Olivia Wills

I am glad you asked Fiona because there is a lot of information out there when it comes to diet and MS, and it can get pretty confusing quite quickly. There are so many different diets being promoted for people living with MS, some with really great intentions, but not all of them are backed by strong or high-quality scientific evidence. And in some of these cases, these diets could lead to some nutritional risks if people cut out important food groups.

So, at this stage, the best advice that we have for people living with MS in Australia is to follow their national dietary guidelines for their age and sex. So, in Australia, that’s called the Australian Guide to Healthy Eating. And this means including a variety of foods from all core food groups. So, lots of fresh fruit and vegetables, whole grains, lean meats, or other protein alternatives like legumes, if someone’s a vegan or vegetarian dairy or calcium-rich alternatives as well.

So, these dietary recommendations are especially important, because many people living with MS also have other health conditions, like I mentioned earlier. So, being overweight or having high blood pressure or diabetes, which we call comorbidities. And these can actually make MS symptoms worse and can actually affect how the disease progresses as well. And these dietary guidelines are designed to help prevent or manage some of these conditions as well.

It is important, I must flag in there, working with a dietitian can be super, super helpful to tailor these recommendations in a way that can support someone’s symptoms, lifestyle and overall long-term health.

Fiona McKay

Yeah, I think that’s really, it’s a challenge for all of us isn’t it in this busy life to maintain those healthy habits. Do you have any guidance Olivia for people who are looking to adjust their lifestyle to maximise brain health?

Olivia Wills

My biggest tip, and I say this to even clients that I see in practice, is just to start with one goal, otherwise it can be quite overwhelming. You don’t need to change everything at once. Pick one thing that feels achievable, whether it’s going for a short walk or adding more vegetables to dinner or setting a regular bedtime. And once that becomes part of your regular routine, then tick that box and we can move on to the next thing. So that way it feels a lot more manageable and sustainable to keep these goals.

And if you’re looking for some guidance, MS Australia launched the Living Well with MS document earlier this year, and that is a great place to start. I was involved in developing the diet, stress management and smoking chapters, and it’s full of practical, evidence-based strategies to help someone make real meaningful changes, but importantly at their own pace.

Fiona McKay

Thank you, Olivia. And those resources will be at the bottom of the episode if you want to look for the Living Well with MS guide, it’s an excellent resource.

So, moving now to discussion with Izanne, I wanted to move to another very important recommendation that Olivia mentioned, and that is the early use of disease modifying therapies and sticking with them.

And as part of World Brain Day, the World Federation of Neurology highlights the importance of early detection and prompt treatment for neurological conditions in general. So regular screenings, checkups and timely medical care catch issues in their earlier stages, they improve outcomes, and they lower the risk of long-term harm. This is also a very important theme in two international MS reports that Olivia mentioned earlier, released in 2015 and 2024 called Brain Health, Time Matters in MS.

And these reports are available for our listeners in the show notes, and they really focus on the importance of this early intervention and regular monitoring of MS activity to make sure that it’s contained as much as possible to protect and preserve the brain tissue.

Now, Izanne is not only an MS neurologist, but she’s done some very interesting research on disease modifying therapies in MS. Izanne, could you please explain for us the concept of early intervention in MS, how the thinking has shifted and how Australian research with the MS Base Registry has really moved the dial on this thinking?

Izanne Roos

So, one of the great advances in multiple sclerosis care is not only the availability and development of therapies that have varying mechanisms of action but also have varying effectiveness. And we now have really good high-efficacy therapies for MS. And we’ve also now learned how to use these therapies in the best possible way to minimise long-term disability and have the best possible outcome for people with MS.

Now the early use of high-efficacy therapies has really been shown to be incredibly important. And we’ve been very privileged in Australia to have access to high-efficacy therapies really early on in a person’s MS disease course. We know that this is helpful because of evidence from real-world registries. And real-world registries like the MS-Base Registry has really led the change and the shift in our treatment approach in MS. In fact, the use of and the evidence gained from real world registries like MSBase has in fact precluded and pre-empted the results for ongoing randomised clinical trials in this area.

So, MSBase is a large international MS registry containing more than 100,000 people with MS and their clinical and treatment information. And this is a registry that was started in Australia and many of our people with MS that are seen at large tertiary MS centres contribute data and have really been pivotal in gaining this evidence. What we have shown over time is certainly that starting high-efficacy therapy as early as possible in the MS disease course reduces not just long-term disability, but also transition to progressive forms of MS. And that this can be even at a delay in four years of starting a high-efficacy therapy, can have significant impacts in the long term.

We’ve also looked at perhaps whether or not there are subgroups of people with MS who don’t need this high-efficacy therapy. So, we know about six percent of people with MS have a more aggressive or severe MS course. And we generally refer to that as people with MS who require a walking aid within 10 years of MS onset. And we studied whether or not people with these features suggestive of aggressive MS, have a greater benefit of early high efficacy therapy compared to people who don’t have those risk factors for aggressive MS. And what we in fact found is that there is similar and equal benefit for the use of early and sustained high-efficacy therapies, regardless of these risks for aggressive MS. In fact, the long-term disability risks are reduced to a very similar degree across these two phenotypes of people with MS. And this very much supports the widespread use of high-efficacy therapy.

Fiona McKay

Thanks, Izanne. So, it’s really important that people are continuing to check in with their neurologist, regardless of how well or unwell they’re feeling, isn’t it?

So, as a person ages, the immune system also ages and there are changes in MS. Now, historically, there’s been a feeling that perhaps people should not be treated with disease modifying therapies beyond a certain age. But some new research from MSBase suggests that perhaps this is not necessarily the case, doesn’t it?

Izanne Roos

Yes, and I mean we know that as we age the immune system changes. The immune system might become slightly less inflammatory. People with MS who age, also develop other comorbidities that anybody in the general population might develop. And as we are diagnosing people with MS earlier and earlier in their disease course, as we get older with MS, people might have been on treatment for quite a number of years before that time.

For all of those reasons, there’s certainly interest in knowing whether or not there is a safe period of time when the treatments that you might have been on for a very long time can be safely stopped or de-escalated. Now, there has been work done using data from the MS-based registry to see whether or not there are safe de-escalation times or safe de-escalation strategies in people with MS over the age of 50 or 55. And unfortunately, similarly, to results from a randomised clinical trial looking at the same question, we have been unable to find a time in which it is absolutely safe to, across the board, de-escalate treatment. And that simply having an older age, is perhaps not a good enough reason or rationale to uniformly stop or de-escalate the treatment response.

Now, I think this is something that needs to be looked at in a lot more detail because certainly we need to have strategies in place as people get older to perhaps look at the treatments that we’re using and see whether or not these can be revisited in a safe way. But based on the evidence we have available to date, I don’t think that a blanket rule saying that once you reach a certain age, treatment cessation would be safe, can be advised.

Fiona McKay

Yep, yep. So again, it’s very important to just be in close contact with your neurologist in a very personalised approach as people age.

Izanne Roos

Absolutely.

Fiona McKay

Thanks, Izanne. Thank you. So, we’ve heard from Izanne about how researchers and neurologists are working to get the best use of the existing therapies in this personalised way to maximise brain health in MS. And existing therapies are based on shutting down the immune attack on the brain and the spinal cord in MS.

But perhaps the greatest unmet need in the MS treatment landscape today is looking for ways to protect and repair the brain. And I’d like to move now to ask Steven about some very exciting work that he’s doing, looking at ways to repair the myelin sheath around the nerves in MS. So, Steve, could you tell us a bit about your research to develop a therapy for remyelination and for progressive MS?

Steven Petratos

Yes, obviously this work has been a considerable body of work over the last 14 years, and we’ve had significant support from MS Australia to be able to continue our work in this space from understanding the fundamental mechanisms of how progression occurs, but then subsequently trying to address that from a therapeutic perspective because we, we’re able to serendipitously identify a small molecule that we are now developing to help stop and reverse MS progression. We have identified specifically that this small molecule can enter the brain and target those cells that myelinate the brain.

And this is really important because that targeted therapy, which is directed towards the oligodendrocytes that are the myelinating cells, through a mechanism that we now know of, enhances their metabolic function. And really exciting outcomes from this research have demonstrated we can protect the brain from the inflammatory damage if we do that.

And this enables us to stop progression of the neurological symptoms that manifest in the animal model of MS. Of course, that’s not…MS…what we see in humans, but we do know that it has the fundamental mechanisms that govern how MS progresses. And we have clearly seen not only the prevention of the demyelination, so in other words, the neuroprotective aspect of the molecule, but we’ve clearly demonstrated now that remyelination can occur in the nerve fibres that have been previously demyelinated.

So that’s a very exciting outcome and a very important finding that we would now like to translate directly into clinical trials and are working very closely with our neurologists here at the Alfred Hospital and of course, looking at incorporating the registries to go towards clinical trials, which we are now setting up and about to launch if we are able to get regulatory approval.

Fiona McKay

Wow, that’s amazing. It’s such exciting research and we’re really, really looking forward to watching this space, Steven, seeing how this develops over time.

So, before we draw our podcast to a close, I’d like to give the last word to our guests. And I’d just like to hear from you where to from here in the MS and brain health space and particularly for your work. Maybe I’ll go to Izanne first.

Izanne Roos

I think that perhaps one of the greatest unmet needs when it comes to MS is targeting progression at the moment. We’ve become really good at stopping new inflammation and stopping those relapses and new lesions. But we now need to look at things that drive ongoing disability progression. That concept of PIRA (Progression Independent of Relapse Activity) that Steven mentioned previously, therapies that might remyelinate and perhaps therapies that are perhaps small molecules can get into that central nervous system space. I think it’ll be exciting to see how these new therapies take us a step forward for people with MS and really optimise that long-term outcome.

Fiona McKay

Yeah, thank you. And Steven?

Steven Petratos

Of course I’m going to reiterate what Izanne just said. Obviously, it’s addressing the unmet need of MS progression and its associated symptoms. If we can stop the disease and hopefully regain some function in people that have lost certain faculties, then the quality of life of people living with MS can be enhanced.

Fiona McKay

Yeah, it’s really the Holy Grail isn’t that stopping and repairing. And Olivia?

Olivia Wills

Now I’m going to take a bit of a different angle to Izanne and Steven and look at it from the consumer perspective. And I’m just so excited to see that brain health is becoming a regular part of conversation for these people. I think it’s so encouraging to see that focus really expanding beyond, of course, the important disease modifying therapies, but conversations about what else is there when it comes to maximising brain health.

And I really believe the next step is making sure that brain health continues to remain the central focus in research and clinical care. But most importantly, giving people with MS the tools and support they need to take charge of their own brain health, whether that be continued education or improved resource accessibility or better collaboration between patients and their providers.

I think all these things are key to really bring that empowerment and change for these consumers.

Fiona McKay

Thank you, Olivia, and thanks so much to all of our guests today for their expertise and their enthusiasm in marking this World Brain Day with a focus on MS and brain health.

And a reminder that for optimal brain health for people living with MS, MS Australia recommends avoiding smoking, staying active, eating healthy, keeping your weight under control, looking after your stress and mood, keeping your mind active, maintaining good sleep hygiene and staying on top of your general health.

And it’s also important to look after things like blood pressure and cholesterol, having regular checkups, including skin checks, pap smears, prostate checks, and ensuring you’re taking your medication as prescribed by your health professional.

Don’t forget to head to our website to read about brain health and MS and our new Living Well with MS guide. Thank you.

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