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.

Rohan Greenland:

I’m Rohan Greenland, I’m the CEO at MS Australia, and this is The Raw Nerve. Today we’re talking about the world’s largest MS conference, it happens every year, this is the 40th year of ECTRIMS. ECTRIMS actually stands for the European Committee for Treatment and Research in MS. It’s the world’s largest MS research conference, expecting more than 10,000 delegates to participate.

This is a preview, ECTRIMS is next week, and I’m being joined today by two very eminent people in the MS research space, our very own head of research, Dr. Julia Morahan, welcome, and also Dr. Heidi Beadnall.

Heidi is deputy chair of our research management council. She’s a consultant neurologist and MS specialist at the Brain and Mind Centre at the University of Sydney, and so a big welcome to both of you and thank you for joining us today to talk about the 40th ECTRIMS Congress.

I’m going to start by asking about one of the really exciting things that’s going to happen to this congress, and that is the McDonald criteria. There’ve been revisions to it, and they’re going to be announced and talked about at ECTRIMS next week. Heidi, what is the McDonald criteria and why is it so important to people living with MS?

Heidi Beadnall:

The McDonald criteria is very important, because it’s the way that we diagnose MS in our patients, both the relapsing type and also the primary progressive type of MS. We’re definitely due for an update, because the last one was in 2017, so the 2024 McDonald criteria we’re certainly waiting for.

Look, diagnosing MS isn’t easy, and I think this criteria is really critical to get it right, really aid us to make the appropriate diagnoses and make them as early as possible, such that we can then start treatment, get the diagnosis right, and start treatments and managements as soon as we can.

Certainly I think the iterations with the 2017 McDonald criteria have been really helpful to that end, and it will be interesting to see with the 2024 criteria, what that adds, and if it adds further to make it easier for us to diagnose MS. That’s I think how it all fits in.

Rohan Greenland:

One of the things that I always think is critical, is it takes so long, we released a report earlier this year that showed it’s almost four years between first perceived symptom onset to a formal diagnosis, and we still use MRI to get that formal diagnosis. How long do you think it’ll be before we can have a simple blood test?

Heidi Beadnall:

Goodness. Look, I think it’s probably still a fair way off, I suspect. Like I often say to people actually in the clinic, I say, “It’s not an easy diagnosis to make.” As you know, people can fit the McDonald’s 2017 and probably the 2024 criteria for MS, and still not have MS, because part of the caveat is that there’s not a better explanation other than MS.

It’s really a ruling in and ruling out, working your way through the investigations to get to as good a case you can for diagnosing MS. I often say to patients, “It would be great if we had one blood test to do this, but with MS unfortunately we don’t. We’ve got to go through this host of work ups to try and get the best diagnosis most accurately that we can.”

I think we’re still a fair way off. I think certainly, some of the discussion points of what we might expect from the 2024 criteria, the use of neurofilament light chain as a diagnostic biomarker and also kappa free light chains as diagnostic biomarkers, have certainly been discussed, but I suspect that they certainly won’t be the answer and won’t be able to give us a single diagnosis. I think we’re still a fairly long way away from having one blood test, unfortunately.

Rohan Greenland:

Well, that’s a really critical area. I think it’ll be really interesting to see the details of the revised McDonald’s criteria going forward. Julia, do you want to comment about that, from your perspective?

Julia Morahan:

I think what we are hoping for is that the new 2024 revisions to the McDonald criteria simplifies diagnosis of MS somewhat, and hopefully we’ll be able to make the diagnosis a little bit more rapidly, because as you say, we still have quite a long time and there is a lot of testing involved, as Heidi said.

The diagnosis does open hopefully the door for treatment for people living with the disease, so the sooner we can get people diagnosed, the sooner we can get them onto treatment.

What I’m hoping for is, a bit of extra information that is part of the criteria, that will allow us to close that gap for people.

Rohan Greenland:

Another thing we’re expecting from ECTRIMS, and we’re very excited about, is another revision, but in 2016 we had the release of the first Brain Health Report and we’re going to see a revised edition released at this ECTRIMS.

Brain health is a concept which is really exciting, and as someone who’s been working in the prevention field for much of my working career, I’m excited about what the Brain Health Report is and what it offers.

What can we expect, what is the Brain Health Report, Julia, and what can we expect to see from this second edition?

Julia Morahan:

The Brain Health Report originally started with the idea, that in MS, and maybe in neurology more generally, we were less concerned than maybe other specialties about the health of the end organ, the end organ being the brain, the organ that’s affected in MS.

It was an idea that was really purported by Professor Gavin Giovannoni in London, and also Professor Helmut Butzkueven from Melbourne. The idea being that we really just need to make sure that we are giving brains the best possible chance of dealing with their MS.

It expanded from there to become a little bit about this diagnosis conversation and about optimal treatment for those people living with MS. It came out with a series of recommendations to try and give global consensus or standards of what we should really be aiming for in the global treatment of people living with MS.

It has been very successful, but as you say, Rohan, it’s been a number of years now, and the criterion for diagnosis has moved along and many more treatments have entered the scene.

What we’re hoping for in this new report is really, what are the policy recommendations and what have we made progress on since that first report? How are we actually treating people better with MS? What impact has that had, and how should we move forward from here, given that we have a whole bunch of new therapies, and also that what MS looks like is changing?

Super exciting, very powerful from an advocacy perspective, and also very powerful in terms of being able to empower people living with MS, to take charge of their own disease where possible.

Rohan Greenland:

MS Australia, in fact, was delighted to be in 2022, the recipient of a Brain Health Award, and so we’re a very invested space, and we have our own resources available for people living with MS. Can you tell us a bit about those Julia?

Julia Morahan:

We do have a number of resources on our website at MS Australia, in terms of treatments that are available for people living with MS, symptomatic treatments. Also, we have guides for people living with MS, and healthcare professionals in terms of modifiable lifestyle factors, and ways that people living with the disease, and their friends and family, can really make sure that they are doing everything they can to manage their MS as well as possible.

We really want people to be their own advocate. A big part of brain health is being your own advocate, making sure that you are being treated as well as possible, making sure you’re getting annual MRI scans for example, and really making sure that if you feel different, if things are changing, that you are the person that goes to your healthcare professional and tries to make change.

We’ve got a whole range of different resources for people, but it’s really about making sure that you’ve got the knowledge and education to help yourself live as well as you can with MS.

Rohan Greenland:

In fact, we know that modifiable risk factors are critical for brain health. There’s often the phrase used, what’s good for the heart is good for the brain. Can you just run through some of those critical risk factors and modifiable risk factors that are important for good brain health?

Julia Morahan:

Absolutely. I think the number one thing that we always say to people is, “Please don’t smoke.” We know that smoking is a risk factor for developing MS in the first place, but we also know from the research, that it will also affect your disease activity. There’s never a bad time to quit smoking, even if you have MS. We would recommend that there is no smoking, please.

Limit alcohol consumption. The usual recommendations there, to try and keep your brain as healthy as possible. Also guidelines around physical activity and making sure that exercise is part of your daily or weekly routine.

There was a bit of misunderstanding about this a long time ago, where exercise were thought not to go together, and maybe it wasn’t the right prescription for people with MS, but we now know that exercise is a huge part of making sure that people are able to manage their MS, and can be incredibly helpful for managing symptoms going forward.

Then, we also have a range of recommendations around diet. It’s a lot about healthy living, and it is as you say, Rohan, messaging that we’ve heard for a lot of different conditions. Keep your weight under control, eat healthily, try and do some exercise. It’s easy to say, more difficult to implement, but we know that it is going to make a difference to your MS.

Rohan Greenland:

We know that ECTRIMS will have a significant focus on lifestyle factors, as it always does, but it’s also, we’ll be looking forward to the next version of the Brain Health Report.

One of the hot topics this year is artificial intelligence and its use in research. Heidi, a lot of your research is focused around the use of imaging and AI, can you explain why AI has really become very rapidly a really important thing in health medical research and particularly in MS research?

Heidi Beadnall:

Yes, look, I think AI is something that’s here to stay in general life, and certainly it has a huge potential to really assist us, I think in health and medicine, and of course that includes neuroimmunology and MS as well.

I think, certainly in health and medicine, I certainly feel the benefits of AI are really going to assist us, I think in the long-term. I don’t think they’re going to take over the people and the clinicians, I think there’s always going to require some human oversight. I really think that utilis ing AI and technology is definitely going to help us going forward, in the clinic and in research as well.

I can see artificial intelligence helping with patient prognostic models, like how are patient’s going to go if you feed in their data? I think you can see how AI can help develop imaging algorithms, which is probably something that has been a particular interest in some of the research I’ve done with my colleagues, and also others forms of patient monitoring, I think AI has a huge potential as well.

I think in terms of probably focusing more down on, using AI to develop quantitative MRI imaging algorithms in MS, which is something I have a particularly interest in, and particularly how these can be rolled out into the clinic. I work with some colleagues at the Sydney Neuroimaging Analysis Center, using AI has actually developed quantitative pipelines that basically measure brain volumes and brain lesion volumes and numbers and metrics that change over time, using a software called IQ-MS.

Basically at the moment, a particular area of interest of research is, I’m collaborating with them to see how we might be able to use this technology in the clinic, and to see how that can assist our clinic appointments and potentially give us extra information to assist, so that’s a particular interest area of mine.

I think in terms of MS diagnostics, I’m not entirely sure if the AI technology and imaging thus far has really played out as well. I think it’s certainly got a huge potential though for monitoring in MS.

It’s very hard for even the best of our neuroradiology colleagues, who are excellent, sitting there comparing scans is very time consuming and any assistance we can give them with some of these AI technologies, I think have real potential benefits.

That’s probably, yes, I’m excited about it, it’s fair to say, and I’m very interested to see what other groups and what other AI technologies will be presented at ECTRIMS, and what people are doing in the research sphere as well.

Rohan Greenland:

Of course, we’re in the very early days, I guess, of using AI to supercharge a whole suite of areas in health and medical research and care, and the future is exciting. I think it’s another tool to help us move forward much more rapidly than what otherwise may be the case.

Heidi Beadnall:

Absolutely, and I think like you said, I really feel there will always be that oversight that will be required from people, but I think if we use these technologies sensibly and use them as an aid, I think there’s a real potential there.

Rohan Greenland:

Thank you, and another really interesting issue that will come up at ECTRIMS is BTK inhibitors. Now, we heard a lot about them two years ago at the time of ECTRIMS in Amsterdam, where there was these promising new therapies in stage two and three trials.

Not so much enthusiasm or excitement about them at last year’s ECTRIMS Conference, there were some question marks about how the trials were progressing, but it seems the enthusiasm is back at this ECTRIMS next week. Julia, tell us, what is a BTK inhibitor and what does it promise to do?

Julia Morahan:

BTK is Bruton’s tyrosine kinase, and it’s an enzyme that is important for B cells, which is an immune cell. There has been a whole suite of BTK inhibitors that have been tested in clinical trials, as Rohan mentioned, with a bit of variable results.

There was a lot of excitement around them, because it is a new class of drug for MS. We have had a lot of immunosuppressive therapies that work in different ways, and this was an entirely new way of trying to treat MS.

We have had a little bit of a sneak peek at some of the findings, but I think what we’re really excited about with the BTK inhibitors, is the potential to treat progressive MS.

We know that we have quite a few medications, and we’re very lucky in Australia to have them subsidised on the PBS for relapsing forms of MS, but for progressive forms of MS, we’re really not able to slow that progression down with the medications that are currently on the market.

The hope for the BTK inhibitors was that we might see some results that show that disability progression or accumulation could be slowed, which would be something really very new compared to what we have in the market at the moment.

Rohan Greenland:

Heidi, as a neurologist, what could this potentially mean for your patients?

Heidi Beadnall:

Well, I think whenever there’s a new drug class that potentially becomes available, I think as Julia has covered, I think the biggest excitement for something like this is that real unmet need of progressive MS, so I think that’s the first thing that probably as a clinician excites me.

I think it’s probably worth also just noting, the studies of the BTK inhibitors in relapsing MS too, because even though the most recent Gemini I and II studies with Tolebrutinib, in relapsing MS, it hasn’t necessarily met its primary endpoint in terms of reducing annualised relapse rates, compared to Teriflunomide.

It doesn’t necessarily mean that that medication doesn’t work, by the way, on inflammation and relapsing MS. It just means that when they’ve done the study over the couple of year period, that compared to Teriflunomide, they haven’t seen a change. I think, it certainly doesn’t mean that it doesn’t necessarily work on that area as well.

I think when you go across to the Hercules study, which is obviously the phase three study, looking at Tolebrutinib in non-relapsing secondary progressive MS, and the fact that it has managed to meet its primary endpoint, being versus placebo, at that six month confirmed disability progression, I think that’s really exciting. Because this is definitely the group that we don’t currently have an effective therapy for, this non-relapsing group in particular, where you don’t have some inflammation.

I think that is really exciting, and I think we really are waiting for the further detail that gets presented at ECTRIMS on this study, so that we can really look down into the nitty gritty of the numbers that are presented.

I think the other thing, as a clinician, that I always keep in the back of my mind, certainly with the BTK inhibitor medication, is that there’s been a little bit of a liver safety preliminary data, there’s been a little bit of liver data, and so I’m really interested from a safety and efficacy perspective to really see that.

I think, a few years ago, with the Daclizumab story, I think I’m always very conscious, just always looking at that safety profile of these new medications too.

I’m really excited about the results. I really want to see more information, but I think after some of the disappointments we’ve had with some of the data with the BTKi’s, this is a bit of a silver lining and a bit of a bright light. Certainly when the primary progressive study also reads out later, hopefully we’ll have some similar excitement.

Rohan Greenland:

Just another reason why ECRIMS ’24 is going to be a terrific congress. One other issue, I mean there’s so many great topics on the agenda for Copenhagen, centers around vitamin D. It’s the Delay Study, we’ve been waiting for this one for a while, Julia, it’s out of France.

Tell us a bit more about what we can expect to hear from the results of the Delay Study, and what are the critical issues around vitamin D, and a lot of interest in, do vitamin D supplements work? What are we likely to learn from this release of the results of the Delay Study?

Julia Morahan:

Very interesting, Rohan, the Delay Study was a clinical trial looking at whether oral vitamin D supplementation in people living with CIS, which is Clinically Isolated Syndrome, so the stage before a formal MS diagnosis, to see whether supplementation with vitamin D could delay onset.

We are very interested in this, as MS Australia, both because we’re really interested in delaying onset and vitamin D, but also because we were the sponsor of the PrevANZ trial, which also looked at whether different doses of oral supplementation of vitamin D could delay onset.

The Delay Study is reporting a positive result, which is incredibly interesting. They gave people a large dose of vitamin D once every two weeks, and they showed that that supplementation significantly reduced the disability accumulation in those CIS patients. They also showed that there was a good safety profile for these very large doses of vitamin D.

This is very interesting for us, because our PrevANZ clinical trial in fact was negative, and we weren’t able to show that vitamin D delayed onset.

I think what we’re expecting, and hoping to speak to the French team while we are in Copenhagen, is there are a number of different methodological differences between the clinical trials, but really the message is that vitamin D is still very much part of the MS story and very much part of the story around the profile of risk factors.

The advice is still the same. We want people to make sure that they have sufficient levels of vitamin D. Oral vitamin D supplementation may be quite important, but we also know that there’s a role for sunlight in there too, and there’s probably something happening with sunlight that’s independent of vitamin D.

Super interesting results from the Delay clinical trial, and we’ll be very interested to speak to the team and see what we can figure out, once we hear the full results from them next week.

Rohan Greenland:

That’s going to be a really interesting report, and will advance our knowledge and understanding of the importance of vitamin D, sunshine exposure, and perhaps earlier access to vitamin D in the life course than previously may have been the case.

Heidi Beadnall:

I think that, as Julia has said, the detail of what the results are that are presented with the DeLay Study will be very interesting, particularly due to the methodological differences and things between the two studies. I think that’ll be really interesting to look at.

I think that, albeit though, the message I think is still the same, I certainly have still been encouraging patients, particularly if they’re vitamin D deficient, or even if they’re in the normal range, try and supplement vitamin D to those higher normal range levels.

As you say, look, these studies are being done to try and give us more evidence for giving this advice, but I think the good thing as well, is that probably having vitamin D levels in that higher normal range is only going to probably be of benefit in terms of MS, in terms of bone and muscle health, and certainly, I think aiming for those higher normal levels, certainly on a clinical day-to-day basis, I still certainly encourage.

I probably don’t necessarily go for those really super therapeutic vitamin D doses, but like I said, maybe that’s what we should be doing, and that’s why we need to keep doing these studies. Yeah, I think it’s definitely still, the vitamin D story continues.

Rohan Greenland:

We’re learning more and more all the time. Thank you both very much. I might just, as Julia sets to pack her bags for Copenhagen, could you mention, it’s not just the formal presentations that are important at ECTRIMS, there’s also a lot of other important meetings that are held in and around the congress. What are you attending and what meetings, side meetings are you participating in?

Julia Morahan:

Yes, that’s right, so ECTRIMS is a really great opportunity for everybody to get together at an international level. MS Australia works with a range of different global initiatives, and ECTRIMS really gives us the chance to meet face-to-face at least once a year, so that’s fantastic.

A couple of different things that I’ll be up to at ECTRIMS this year, will be meetings of the scientific steering committee of the International Progressive MS Alliance, which was set up as a global body to really try and supercharge the research towards treatments for progressive MS.

This is the one time a year where the scientists and the scientific research staff and also the industry forum, can meet to really talk about all of the issues and the work and activities that we’ve been doing over the past year.

It’s also a great opportunity for the international group to meet around our global research strategy, which is known as Pathways to Cures. We’ve just recently published an update to that global research strategy, but really mapping an opportunity for us to map what’s going to happen over the next 12 months with that global strategy and the work that needs to happen, that will sit underneath that.

Really lovely to be able to do this face-to-face. We have a lot of Zoom calls during the year, but it’s very nice to have everybody in the one room and talking about all of these important things.

I think the nice thing about ECTRIMS is that everybody is in the one place, so we will definitely be catching up with the Octopus team, talking about our plans for getting so close to the launch of recruitment on the Australian sites, so it’s a great time for us to be able to see them and just fantastic to be able to have those conversations face-to-face.

Rohan Greenland:

Well, ECTRIMS is going to be terribly exciting. We look forward to your tweets and posts on social media, from this magnificent and terribly exciting congress. Now, just the only thing I’ve got left to do is to formally thank both Julia and Heidi for your contributions today, and we’ll be all ears for ECTRIMS next week.

Julia Morahan:

Thanks so much.

Heidi Beadnall:

Thanks very much.

Voiceover:

Thanks for listening to The Raw Nerve, the official podcast of MS Australia. To hear more, subscribe to our podcast today, at msaustralia.org.au/podcast.