We have the pleasure to have with us now, Dr. Günter Höglinger coming from Munich in Germany. And he's an expert in PSP Tauopathies and also in general in Parkinson's disease and in atypical Parkinsonism.
So today we're going to discuss what are the main novelties, what are the highlights in the world of PSP Tauopathies and atypical Parkinsonism. So first of all, thank you for joining me today. What do you want to share with our listeners? What are the major things that are happening in the field of atypical Parkinsonism that are pushing the field forward?
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[00:00:51] Dr. Gunter Hoglinger:
Yeah. We had a number of new, different presentations here on PSP and related diseases. So it's difficult to actually to focus because the field is so dynamic.
Let me briefly start with genetics. There is a couple of new papers out on the Genetics of PSP predisposing for the disease. There is one genome wide association study with larger numbers than ever before and, most of them being autopsy confirmed, so really solid evidence. And then there is a first genome sequencing paper also outpublished and, both of them confirm what we knew already, namely that common variation at the tau locus predisposes for the disease.
So It's really a primary tauopathy, a really good prototypical disease to study tau targeting therapies. And there is some interesting novel findings that arose on a new risk loci that have been identified. One which I find particularly intriguing, you know, that APOE4, for example, is associated with Alzheimer's disease. We know now that this is actually protective against PSP, but APOE Epsilon 2 is a risk factor for PSP. So commonalities and distinctions within the larger group of tauopathies. That's one of the major findings.
And then also more fine grained knowledge about genetics of PSP tells us that inflammation is also playing a role. Complement activation has been identified as one of these factors that are associated with PSP. So maybe you want to check out the papers that are all published. And a new paper is already on a preprint server, just under development. evaluation for for publication in a peer reviewed journal about copy number variation in PSP.
So a lot ongoing that's genetics.
[00:02:36] Dr. Michele Matarazzo:
Very interesting. What else? What else?
[00:02:38] Dr. Gunter Hoglinger:
Well, then we had a lot, about imaging. Now we know that MRI imaging is very successful in PSP. You can actually see atrophies at baseline, which helps to guide diagnosis. Then you can also track progression of the disease over longitudinal serial images within short periods such as 12 months, 18 months. That's really a cool thing to monitor biological advances in the disease and also to see whether your therapeutic interventions can modify the course of the disease.
There is now one very new paper from Andrea Quattrone online, for example, from Italy, who pulled a lot of available data sets, And then, checked which of the parameters to monitor progression is actually most suitable to track progression with a small number of patients. So this is online published in the Movement Disorders journal a couple of weeks ago. Maybe you want to check that out.
And then, this is morphology. So this is atrophy. Then there is one very first paper out which compares the Diagnostic value of FDG PET, so a functional imaging, measuring metabolism of the brain in contrast to mRI measuring atrophy, so brain volume loss.
And there is as a conclusion a algorithm proposed which says that especially in diagnostically equivocal cases where MRI doesn't really help you and clinics doesn't help you, FDG PET might actually really also provide added value. Very cool paper. So that is, that is interesting.
And then the new kid on the block is, of course, Tau imaging, Tau PET. There is a couple of traces that are in the pipeline. One, which I find particularly interesting is at the forefront of the publication, at least numerically, from the papers that are coming out, that is PI 2620, and, there is a lot of papers showing, that it might help for diagnosis. It might help for progression monitoring, that it coincides with hypometabolism, it coincides with inflammation in the brain, and it coincides also with the region specific symptoms that patients experience.
So a lot of new things that are out there. I think this will position functional imaging, tau imaging also at the center stage of future clinical trials.
[00:04:51] Dr. Michele Matarazzo:
Well, this is very, extremely interesting and definitely all of these things are going to be very useful for the future of helping patients, clinical trials, and helping understand what is happening in the brain of people having these diseases.
And something else that you you probably want to mention is also at the biological level, if we are able to detect these proteins and if there is any novelty from that point of view.
[00:05:17] Dr. Gunter Hoglinger:
Fluid biomarkers or biomarkers in tissues that we can measure. I think that's also very exciting.
There was one junior award, which was awarded to Edwin Jabbari from London, indeed, which was one of the first reports, not the first, but one of the first reports actually to suggest that a seed amplification essay also works with four repeats tau, or four repeats tauopathies, including pSP. There is already published paper suggesting that this could work in post mortem brains. There is one published paper suggesting could also work in cSF. And now there was Ed Jabbari's work who combined, actually, tau and sinuclein seed aggregation in order to guide differential diagnosis. That's super exciting.
Also, Gabor Kovacs has just one paper which has just come out two weeks ago online, suggesting that seed aggregation for 4 repeat tauopathies might also work in the skin. So, I think we're getting closer to a biological diagnosis, and we have just published a paper a couple of weeks ago in, nature Medicine, which makes use of extracellular vesicles and the tau content therein, particularly two different isoforms, 4 repeat, 3 repeat, and the ratio thereof in extracellular vesicles, which you can retrieve in blood, which are derived from the brains of the patients that might also help to identify patients. So a blood or skin based biomarker would really be a very useful tool, also non invasive, easy to achieve. If that is confirmed in larger cohorts and independent laboratories, I think that's real game changers.
[00:06:48] Dr. Michele Matarazzo:
Yes. Well, very much, Gunter, for, for being with us today. It's been a pleasure to have you and thank you for sharing with us all of these novelties.
And hopefully some of them when we will discuss again next year will have advanced even more. And so we will be able to see how they will actually be able to be applied in clinical practice.
And thank you all for listening.