Update from the Synuclein Meeting 2022

[00:00:30] Prof. Veerle Baekelandt:
I'm fine. You?
 

[00:00:32] Prof. Tiago Outeiro:
Have you recovered from the organization of the senior clean meeting this year?
 

[00:00:37] Prof. Veerle Baekelandt:
Yes. Yes, and no, of course. It was lots but I am happy that everything went well. Of course it also means that some my other work was piling up. I'm not having a very busy time to catch up.
 

[00:00:55] Prof. Tiago Outeiro:
Yeah, I can imagine. So what are the synuclein meetings? When did they start and what are the goals of these meetings? Can you tell our listeners a bit about these meetings?
 

[00:01:05] Prof. Veerle Baekelandt:
Yes. I was not involved in the f irst meeting. So I only participate, think, the last meetings. They started, about 14 years ago, 15 years ago, if I'm correct. And so it was a kind of informal initiative from some scientists who thought that it would be good to have a focused meeting on this protein because of the increasing importance of this protein.

And it was decided to have two yearly meeting focusing on alpha-synuclein, mostly from a basic scientist point of view, but also with interaction with clinicians. But it's, it's really supposed to be a scientific meeting. And the idea is to have interactions and discussions new discoveries new insights and the role of synuclein related to disease, but also basic role of this protein.

 They have become, I think, increasingly successful because they started very small, and they are still small, but now we were about 250 to 300 participants at the last meeting.
 

[00:02:14] Prof. Tiago Outeiro:
So the program was intense and covered a variety of areas. what would you highlight from, from your perspective as an organizer, as the biggest news of the meeting?
 

[00:02:24] Prof. Veerle Baekelandt:
Yeah. I think it's a very difficult question because indeed there was a lot of exciting news really at different levels. So I also think that there was not like one biggest news. I think there were some highlights that even come from different groups. So I think there's some new themes or emerging teams that are present in the synuclein field .

I think it's clear that, and it's not only in this meeting, but the last years, it's clear that the focus for syneuclein, which was until recently mainly on the brain and neurons, is shifting towards periphery. So outside of the brain where we will look at certainly immune system and even an active role of alpha-synuclein in the immune system. So not only that it interacts with the immune system, but I think it's becoming clear that it's really has an active role in immune response and that's I think new insights.

Also the periphery importance of the gut, the intestinal system and the role of alpha-synuclein there as a kind of early sign in, in Parkinson's disease is something that is becoming increasingly clear.

I think there's also some new technologies that have led to new insights and it's really sophisticated technologies like super resolution imaging or cryo em, single cell sequencing that give a detailed view on, for example, the structure of alpha synuclein. So it's clear that the aggregates of alpha-synuclein the fibrils, they're not one structure, but that they are really different structures and they seem to segregate according to disease. Like, in Parkinson's disease and multiple system atrophy they seem to be different, but it's, it's also not one structure. So I think that that's a, a challenge for the next year to try to understand the relationship between structure and pathology or function. I think that's also one of the new insights.

I think that what is also important is that alpha-synuclein should not be seen in a cell on its own, but that it's really interacting with membranes. The importance lipids and lysosomes also something that is becoming increasingly clear.

So I think that's more or less what would think as some of the highlights the meeting.
 

[00:04:59] Prof. Tiago Outeiro:
Yeah. And there was also an intense debate about the actual relevance of synuclein pathology in disease. And so what do you think we, we still need to do in terms of understanding biological function and also it's role in pathology PD instances. How do you see this? Do you favor one side over the other, or where do you stand?
 

[00:05:24] Prof. Veerle Baekelandt:
Well, I think it's very good for the field that scientists remain critical and go back to the original assumptions and look if this is really what we think.

So, indeed there were some opinions of, if you look at very detailed facts on, for example, the importance of alpha-synuclein in synapses and synaptic function that you could say that even if you take out alpha-synuclein synapses are still doing more or less okay. So you could say, well, it only has a minor importance in synaptic physiology. Also, if you look then on the other side to human, postmortem material like Glenda Halliday lecture on is alpha-synuclein really necessary for Parkinson's disease and other syneucleinopathies. If you look objectively at all the material, you can actually dissociate alpha-synuclein from the dopaminergic degeneration. So there are some cases, and not only some cases, but then, so you could say that there's not a direct correlation between alpha-syneuclein pathology, and then the symptoms or the diagnosis of Parkinson's disease. So that's of course something that is intriguing.

I think it doesn't mean that alpha-synuclein is irrelevant. I think everyone agreed on that, but maybe the relationship between alpha synuclein and disease or alpha-synuclein and synaptic function is not as straight forward as we would like to think. So it's just more complex and, yeah, I think it's a challenge, but it gives us new ideas on being critical on ourselves and to move forward.
 

[00:07:09] Prof. Tiago Outeiro:
And so, as an expert in the field, what are your major expectations for the next one or two years? What major issues do you think we'll be able to solve?
 

[00:07:19] Prof. Veerle Baekelandt:
I think there are some exciting evolutions in the field. Also at different levels, there's this very large initiative that's called PPMI where a large cohorts of patients are followed. And the idea is to look at diagnostic markers and markers of progression.

And I think in the coming years, it will become clear if we will be able to have good, reliable markers. And that will certainly be very important for patient's diagnosis, but also for following up of some new therapy. So that should be something over the next years that will become clear.

What, what will also be I think important is that there are some clinical trials ongoing, and I think the next years it will become clear whether we are on the good track with these trials are not. And they're Alpha-synuclein based, but also in LRRK2 based. And I think it's very exciting to see these trials and some might probably be negative, but, I think that give us some new leads on more rational therapies or not pure symptomatic therapies, therapies that we try to halt the progression of the cause or the cause the disease. So that's also something That I What I also mentioned about the structures of alpha-synuclein. I think that's also a very I expect the next years will become clear how this might more targeted therapies.
 

[00:08:53] Prof. Tiago Outeiro:
At the meeting, we had several patient organizations present and we had the participation of individuals with Parkinson's. This was fantastic, I must say. So what feedback did you get from those participants about the meeting? How do they come to such a specialized meeting, probably hearing things they don't always fully understand. So how do they feel about getting in these meetings?
 

[00:09:19] Prof. Veerle Baekelandt:
Well, in my view, they are very positive about the meeting. Of course, most of them are not real scientists at some level they say it's probably too specialized to understand but I think they are very motivated and they also are really supportive of new research and to see how this can lead to some solution.

So I think it's, it's from both sides. For the patients, I think they feel more involved if they can come to a meeting of scientists. For the scientists, think it's also very important, certainly for the young scientists, to be aware of how urgent it is, how important it is to collaborate and to join forces. And I think the interaction, is really something we wanted to promote, and we are very happy that we could do this.

Of course maybe we should also make clear to the patients and to the clinicians that, it is very complicated. So alpha-synuclein, even this small protein is a very complex object to study.

And so we should also not give false hopes, I think, patients. Even if we work hard and we are progressing, it does not necessarily mean that within one year we will have the perfect solution, and probably not. It's becoming more clear also that the disease is very diverse and we might go to more individual therapies, where not one therapy will be possible or useful for every patient. So that's also something that might be a bit disappointing for patients that there will probably not be a miracle solution for all patients.
 

[00:11:03] Prof. Tiago Outeiro:
Yeah, that's true. Can we get some inside information on where the next alpha-syneuclein meeting might take place?
 

[00:11:10] Prof. Veerle Baekelandt:
So the date has not been set yet, but normally it's every two years. So we expect that it will be in 2024. But it will be in Cambridge, which is of course a very nice place to organize it.
 

[00:11:25] Prof. Tiago Outeiro:
Great. So our listeners can stay tuned and keep an eye out for Cambridge 2024. So thank you so much for your time. It has been a pleasure having you with us on the MDS Podcast.

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