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International Parkinson and Movement Disorder Society
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Highlights in Progressive Supranuclear Palsy Research | Congress 2023

September 18, 2023
Series:MDS Congress 2023
What direction will the field of PSP research go in the years to come? Prof. Gunter Höglinger sits down with Dr. Eduardo Fernandez at the MDS Congress to help answer that very question. 2023 Congress virtual access

2023 Congress virtual access

[00:00:00] Eduardo de Pablo-Fernández: Hello, and welcome to a new episode of the MDS podcast, the official podcast of the International Parkinson and Movement Disorder Society. This is a special edition of the podcast from the MDS Congress in Copenhagen. And I have the pleasure of introducing Professor Günter Höglinger from University of Munich to discuss the highlights on progressive super nuclear palsy research.

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Gunter thank you very much for your time and welcome to the podcast. 

[00:00:35] Dr. Günter Höglinger: Yeah, thank you. Very pleased to be here. 

[00:00:37] Eduardo de Pablo-Fernández: So it's the first day of the Congress. We will start discussing the highlights from the previous year or couple of years on progressive suparanuclear palsy. There has been advances in the diagnosis and also ongoing therapeutic trials with promising results. Would you like to give your view about the research highlights on this field? 

[00:00:58] Dr. Günter Höglinger: Yeah. Thank you for that [00:01:00] question. I think we have the pleasure to live in very exciting times. Especially in the field of tauopathies, PSP, CBD. There were numerous breakthroughs that we were witnessing in the past years. I think one of the big achievements in the last years was the proposal by Michael Gooder and colleagues that cryoEM analysis of the structure of tau can actually serve to classify tauopathies on a molecular basis. That provides a biological basis for classifying tauopathies and objective classification rather than by clinical syndromes. And I think then will also help to provide tools for molecular diagnosis and molecularly-targeted therapies in the future. 

Then another area of exciting research is Tau PET, where we also observe that different ligands are popping up, which are originally more designed for the field of Alzheimer's disease, but also in the field of tauopathies, there is some utility, especially with the ligand [00:02:00] PI-2620. I think there were exciting findings showing that tau is spreading along axonal transport processes. That was data published by Meyer et al. in Nature Communications in 2022. There is more exciting data to come.

Then we were witnessing two exciting clinical trials, the Abbvie trial with Tilavonemab end terminal tau antibody, which showed great recruitment and great performance of the scales and tools that we had per plan. Unfortunately, no clinical signs of efficacy, but I think the trial showed that we as a community are ready to perform such trials.

And the second parallel trial, which was recruited in parallel with the Gosuranemab antibody, also an end terminal tau antibody developed by Biogen, was also a very exciting show case of the performance of the community. 

Then we have the academic cohorts, which I think are very excited. There is ALLFTD in the US, there is PROSPECT-UK, there is DESCRIBE-PSP in Germany. [00:03:00] And all of these large natural history cohorts provides data that are very helpful to plan for the clinical trials, especially not only focused on Richardson syndrome, but also on the variant PSP phenotypes.

So that in, in my perspective, are the major important developments of the past couple years. 

[00:03:18] Eduardo de Pablo-Fernández: Thank you for that great overview. It's exciting times to see not only that we are witnessing these advances in defining the tauopathies, but also seeing that there is clinical trials in development . From what we have seen in the last couple of years, it seems that there's been a great shift from the clinical definition to then molecular definition. And that is obviously leading to more precise clinical trials with the potential of modifying the disease course. What is the direction of PSP research in the years to come? What is expected in the next few years in terms of progression to molecular diagnosis, and also to therapeutic clinical [00:04:00] trials? 

[00:04:00] Dr. Günter Höglinger: As you just point out, we have learned a lot about clinical phenotypes and we are about to generate the natural history of the distinct phenotypes.

That's, I think, a very important work that needs to be followed up further in order to enable also non Richardson syndromes variant to be recruited for clinical trials. I think that's ongoing and that's on a very good way. On the other hand, we have the urgent need to define the diseases more on a biological basis. And there we hope and see very exciting developments also on fluid biomarkers. There is exciting ongoing work, on tau seeding aggregation assays. Not yet to the point, as with alpha-synuclein, but I think we're on a very good path and expect quite meaningful results in the next couple of years. Then there is measurement of distinct tau specimen and blood CSF exosomes that's also very exciting to be followed.

And of course there is ongoing omics studies in different biofluids where we also expect some important insights into biological definitions and [00:05:00] biological diagnosis of PSP. 

With regard to imaging biomarkers, I think the MRI data were already quite helpful in the past clinical trials. Now we and others are doing artificial intelligent approaches to get even better insights into diagnostic prediction and progression performance of these data sets. 

Then very pleased also to see that there is an upcoming phase three trial with the Tau PET Ligands that aims to be approved by FDA for use as a diagnostic tool in PSP.

And even more exciting maybe, there is also a move from preclinical to clinical development of four repeat tau specific PET ligands. So whether or not they will do their job as promised, as hoped for, remains to be seen. But already the fact that we are entering into that phase is very exciting.

With regards to making use of that information for clinical trials, we hope for good outcomes of ongoing clinical trials. There is the U C B sponsored trial with the Mid [00:06:00] tau region antibody Bepranemab a phase one trial where we hope to see data very soon. Then there is the ongoing c neo study with a tau targeting antisense oligonucleotide from Novartis. Also phase one B trial where we hope to see data very soon. And there is a French company called ALS Protect with a progranulin secretion in increasing substance called ALS Protect 2006, where we also hope to see data very soon. 

So this is the ongoing studies and then there is upcoming studies.

Amylyx you know, there was AMX35 approved for ALS treatment by FDA. They are now going into a phase three trial, also with PSP patients. Farrer from Spain is taking up the OGA inhibitor, developed originally from Asen neuron, also going into a phase three trial. Very exciting to see.

And then there is very early developments also on cell and gene therapy. So there is quite a number of different approaches also into the anti-inflammatory [00:07:00] pathways. So the pipeline is full and very exciting to live in exciting times.

[00:07:04] Eduardo de Pablo-Fernández: Absolutely. It's exciting to see so many clinical trials with so many different potential pathogenic mechanisms involved.

I think one of the challenges of research on PSPs is I, I think I see PSP and CB D, the tauopathies, as the quintessential Heterogeneous clinical disorders known. As you mentioned, some of those more rare phenotypes are still not included in clinical trials. And I think probably that's one of the challenges ahead.

 I think international collaboration is needed to develop potential medications. 

[00:07:37] Dr. Günter Höglinger: Rare phenotypes are for rare disease, so that that only works in international collaboration as a setting. 

[00:07:43] Eduardo de Pablo-Fernández: Excellent. So this is the first day of the Congress with an exciting program ahead. What would be your highlight of the program, regarding PSP? 

[00:07:52] Dr. Günter Höglinger: I think there is two major events. The first is the meeting of the MDS-endorsed PSP study group. There is one major [00:08:00] change after several years of leadership. Me, myself and Maria Stamelou will hand over the leadership to Huw Morris, Gabor Kovacs and Yarsolau Comp ta. I think that's very exciting because they are known for that dynamics. They have very complimentary research orientation and they are from different countries. So that will give new momentum to the field. 

And then there is an exciting plenary which focuses on new developments on MSA and PSP and Gabor Kovacs from Canada will present on PSP, so don't miss that. 

[00:08:32] Eduardo de Pablo-Fernández: Exciting meetings that the listeners can see on demand in the future. I have to congratulate for your leadership on the PSP study group. I think it's been a very successful period. 

Thank you very much for your time here during the Congress, and thank you everyone for listening. [00:09:00] 

Special thank you to:

Prof. Gunter Höglinger
Professor of Neurology & Translational Neuroscientist
Ludwig-Maximilians-University Munich
München, Germany

Eduardo de Pablo-Fernández, MD, PhD 

Department of Movement and Clinical Neurosciences, UCL Queen Square Institute of Neurology, London, United Kingdom

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