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International Parkinson and Movement Disorder Society
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Special Issue - Biomarker Updates: A conversation on biomarkers and diagnostics of Parkinson's disease and related disorders

April 01, 2024
In this episode, Dr. David Burn shares his views with Prof. Tiago Outeiro on the topic of diagnostic and biomarkers in PD and atypical parkinsonism, and how these may impact the clinical practice. Recorded at the MDS-ES Focused Workshop: Diagnostic and Progression Biomarkers in Parkinson’s Disease and Atypical Parkinsonism, Feb. 29 - Mar. 02, 2024.

[00:00:00] Tiago Outeiro: Hello and welcome to the MDS podcast, the podcast channel of the International Parkinson and Movement Disorder Society. I'm Tiago Outeiro, a professor at the University Medical Center Göttingen and Newcastle University in the UK, and today I have the pleasure of being with Dr. David Burn, a neurologist at Newcastle University and president elect of the MDS. So David, thank you so much for taking the time to speak to our podcast. And we are here in Padua at the moment at this workshop on Diagnostic and Progression biomarkers of Parkinson's and Atypical Parkinsonism. So it's great to have you here. I would like just to get your thoughts on a few questions related to the topic.

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 As you know, and this is why we're here, biomarkers are now a very hot topic in Parkinson's disease and related neurodegenerative diseases. How do you see the times you're living and the opportunities coming about from the use of [00:01:00] biomarkers? 

[00:01:00] Dr. David Burn: Great. Well, it's a pleasure to be here, Tiago. And thank you for speaking and putting me on this podcast.

I mean, it's been a wonderful conference so far. And I have to say, it's incredibly timely because the whole field of biomarkers is a really hot topic at the moment. I think all of us see biomarkers as a way of trying to stretch our boundaries, hopefully in the area of diagnosis and not only just earlier diagnosis, but also in accuracy of diagnosis, which I think is going to be absolutely critical.

I think beyond that, we all hope that biomarkers will give us some sensitive measures in terms of measuring disease progression more accurately. And of course, the beauty of that is that they're willing to inform the size of studies required far more accurately than perhaps we can currently do.

That will, I'm sure, make studies, for example, more cost effective. And again, related to that, I think the use of biomarkers to maybe better understand the [00:02:00] underlying pathophysiology, biological mechanisms will mean that we can probably move genuinely towards an era of targeted precision therapies for the treatment of people with these awful neurodegenerative diseases.

[00:02:14] Tiago Outeiro: Thank you. So you touched on the use of biomarkers essentially as a research tool, but do you see that we are close to really using them in clinical practice, or do you think we're still not quite there? 

[00:02:26] Dr. David Burn: Yes, that's a great question. I think we should look at the biomarkers not as a homogeneous entity because we obviously talk about wet biomarkers, dry biomarkers and so on.

And I mean, in many senses, we've been using biomarkers in the form of imaging for many years. I think the problem in that domain is that the sensitivity and the specificity has been somewhat lacking. When we then look, for example, at other, which again are featuring in this meeting, the functional imaging biomarkers, [00:03:00] then that takes things up a level, but then you run into the problems about availability and where such tests can be carried out.

From the wet biomarker side, which we've heard a lot about in the sessions that we've attended so far. I think that we're not quite there yet , but I think it's within touching distance. And I think I heard somebody mentioned maybe within the next two years, three years, something will be coming through that may be far more applicable in the clinical setting.

I think that is absolutely within reach. So yes, think it's tantalizing. I hope that by the time I'm retiring that there would be these tests available. The big concern we all have, is that MDS is an international organization, and we would hate that there would be an unintended consequence of all of this, which is, as I think implied in your question, that this would be confined to only a few small elite centers or more [00:04:00] affluent countries, and we would hope that these kind of tests will ultimately be available to as many people as possible and be affordable in the process. 

[00:04:08] Tiago Outeiro: You're touching now on an important challenge that we may face in the future. But what do you think are still additional challenges we're facing in this field of biomarkers? You touched on imaging as a biomarker that we've used for a long time. Of course, now we are thinking a lot about the alpha synuclein seed amplification assay.

But even if we go beyond that, what kinds of challenges do you think we still need to solve? In order to really be able to use a biomarker that could actually be a combination of markers. 

[00:04:38] Dr. David Burn: Another really great question. And I think you may have put your finger on it at the very last comment there about ultimately it may be that a combination of biomarkers is going to be necessary here.

I'm reminded of the conversation we've actually had at this meeting, which I know it's a contentious thing as to whether we would regard, say, testing for genetic profile of a patient [00:05:00] as being is that a biomarker or not? Some might argue, yes, and there was a very interesting debate around how one interprets variants of unknown significance but the very fact is we know that in certain countries, patients are already coming along with readouts and asking their neurologist, how do I interpret this?

And therein encapsulates a big challenge that we have with biomarkers. And what are we going to run into issues of false positives, false negatives and so on. So that's the problem. Reproducibility is a big issue with all of this. I know there's been a lot of debate about the diagnosis of Parkinson's at the moment, and I guess implicit in that is the significance.

You mentioned the seed assay for alpha synuclein. I think we're still trying to establish what the real role of alpha synuclein is, for example, in the pathophysiology of Parkinson's. So we might end up sending ourselves down a proverbial rabbit hole if we're not careful by putting too much emphasis

on a [00:06:00] particular protein or a particular test where in fact it may not necessarily be really highly representative of what is going on at that cellular level within the brain. 

[00:06:10] Tiago Outeiro: I would like to ask you what you're thinking about the workshop so far, and if there's anything you'd like to highlight from what you've seen so far. 

[00:06:16] Dr. David Burn: I've been so happy to have accepted the kind invitation that I got from yourself and Angelo to attend this meeting. It's been really high quality. I mean, we're obviously not all the way through yet. So it's a bit invidious to pick out talks because obviously we've got more than, well, at least half the program to come, I think.

But I was particularly impressed by Günter Höglinger's overview last night of P, both from a biomarkers perspective and then on the back of that, some of the new therapies that were coming through. I still remember sitting in clinic and about the only time I've ever seen a really excellent specialist nurse cry was in an atypical Parkinson's clinic with the lack of treatment that we had to offer [00:07:00] these patients.

 It gives us all real hope, and that's what I took from that talk. Today, I really enjoyed the genetics session. I thought it was a wonderful update, and it really was so cutting edge. And the conversation, the discussion that was had afterwards, which I've referred to, was really good. I mean, it was challenging in a respectful way, but it was really good as to how we interpret these kind of readouts and how ubiquitous genetic testing should be.

[00:07:26] Dr. David Burn: And then, obviously, we've just had our keynote with Wilma D.J. Van de Berg from the Netherlands and her elegant work looking at the structural layout of Lewy bodies. I've seen pictures of Lewy bodies before and their general infrastructure and the components. But nothing like she showed, it really blew my mind.

These are not random bodies that come into being, they are highly structured and that's obviously going to raise a whole series of other questions as a consequence. So as I say, it's invidious to pick out certain talks because the whole program has been brilliant [00:08:00] so far and I'm sure the rest will be too, but they're things that have sort of stuck in my mind.

[00:08:04] Tiago Outeiro: Wonderful. Thank you so much for sharing your thoughts and thank you again for taking the time to talk to our podcast. That was a great pleasure. 

[00:08:10] Dr. David Burn: You're very welcome. Thanks, Tiago. 

[00:08:13] Tiago Outeiro: So we've just interviewed Professor David Burn on the occasion of the MDS-ES workshop on Diagnostic and Progression Biomarkers in Parkinson's Disease and Atypical Parkinsonism in Padua.

And so I want to thank you all for listening and I invite you to join us in our upcoming podcasts. 


Special thank you to:

Dr. David Burn, FMedSci, MD, FRCP
Faculty of Medical Sciences
Newcastle University
Newcastle, United Kingdom

Tiago Outeiro, PhD 

Director of the Department of Experimental Neurodegeneration 

University Medical Center Goettingen, Germany

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