Today, I have the pleasure of speaking with Dr. Andrew Siderowf, Hertig Stern Professor of Neurology at the University of Pennsylvania. And we're going to be discussing the pathophysiology and treatment of Parkinson's disease as part of our special Congress 2024 series. Welcome to the podcast and thanks for speaking to us today.
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[00:00:51] Dr. Andrew Siderowf:
So I think that 2024 follows the course of 2023 and Synuclein based biomarkers seem to be a really important theme across both of these years.
In 2023, there was a lot of interest in the CSF based synuclein biomarkers, especially the seed amplification assay. I think we've seen more understanding about how the seed amplification assay helps classify patients in 2024. The big change in 2024 is we saw skin based synuclein assays is just the simple immunohistochemistry really an application of techniques which have been available for a number of years, but were refined in a way which made them sensitive and specific measures of synuclein pathology in the brain.
And this has been a major breakthrough for identifying synuclein in peripheral tissue. And I think been interesting for patients, and patients, I find, have been much more enthusiastic about having a skin biopsy than I have been about having a lumbar puncture, which you can imagine. I still think there's a role for the CSF, because I think it gives information potentially that the skin doesn't give, but having a peripheral biomarker for synuclein pathology has been a big change.
And So I think that this biomarker has been very important. I think that what we're hopefully looking for towards the future would be a synuclein based imaging. There are a lot of different groups that are working to develop alpha synuclein PET and SPECT tracers. But this has been going on for a number of years now.
And although there seems to be more progress now than there really ever has been, there hasn't been a definitive synuclein tracer for Parkinson's disease. I think we've seen real progress in synuclein tracers for MSA. But even that field has a way to go still till it's widely useful in clinic.
But I think imaging biomarkers for synuclein will be the next phase following these fluid based biomarkers.
In terms of the application of these biomarkers, we've seen a lot of interest in biologic classification of Parkinson's disease, and several groups have put, put forth ways to think about the biological underpinnings of Parkinson's disease either in descriptive schemes or in classification schemes, and There's been, I think, a certain amount of controversy about how these different systems line up with each other. To me, I feel like the basic concept that they try to understand Parkinson's disease as a biological entity rather than as a biological entity which is characterized by specific pathology rather than a clinical entity, is really the core thing that unites them.
And the differences, I think, are, have been drawn a lot of attention, but probably less important in the long run than the commonalities.
[00:03:38] Dr. Sara Schaefer:
And from a treatment perspective, anything that has been particularly notable?
[00:03:42] Dr. Andrew Siderowf:
I think, The thing that was notable for me and my patients was the fact that we were hoping to see pump therapies around the middle of the summer and the FDA didn't approve either of the pumps that were up for consideration at that time.
And it was disappointing for patients but I think that, you know, the FDA obviously needs to consider safety and have a thorough process, and we we understand that. I do hope that the companies and the FDA can come to terms and we can see these therapies available for patients before too long because it is a major unmet need.
[00:04:21] Dr. Sara Schaefer:
And it is starting to be used in other countries outside the United States,
[00:04:25] Dr. Andrew Siderowf:
As close as Canada.
[00:04:26] Dr. Sara Schaefer:
Yeah. All right. And have there been any sessions so far that have piqued your interest regarding Parkinson's pathophysiology and treatment at the Congress or any upcoming sessions in the coming days that you are particularly excited to see?
[00:04:43] Dr. Andrew Siderowf:
So this morning, I'm a professor at the University of Pennsylvania, and I've had the pleasure of knowing Virginia Lee and John Trojanowski, her late husband, for all of my career, but I've got a chance to listen to Virginia give her. Presidential lecture today and it was just terrific. She's wonderful and I was, always learn something.
And the rest, and then I went to the session on Alpha synuclein biology, which I thought was just terrific. The talks were really interesting. And I learned a lot there too. And going forward, I'm Khatabi give the keynote lecture tomorrow. Her, she's an expert on artificial intelligence.
She's been working. On Parkinson's related problems and I think it's a really exciting part of the program that we bring people from related adjacent fields who are world class experts to talk to us about their work and connect it back to what we can potentially learn from them and also then apply in our field.
So I think this is a wonderful part of the program that we have not just people that are in our field but also people who are working in adjacent fields that we can learn from and cross pollinate.
[00:05:51] Dr. Sara Schaefer:
So, what do you think are your take home points for our listeners and, and similarly what do you think is up and coming in the rest of 2024 and 2025 if you add a crystal ball?
[00:06:04] Dr. Andrew Siderowf:
So if, I think that related to biomarkers and biologic classification, I think we're going to see some a meeting of the minds, some a combination of these two competing systems so that they can sort of coexist as they, as they naturally really should. And I think that thinking about Parkinson's as a biologic entity will certainly help with drug development.
I think thinking of it as just exclusively a snuclein problem may be a bit narrow because it's really important to consider that the snuclein
needs to have underlying pathomechanisms in order to accumulate in the first place. And also there's an important role for coexisting non synuclein pathology in patients with Parkinson's disease, both concomitant plaques, amyloid plaques and tangles but also tau pathology, potentially TDP 43 pathology.
And these things are also, maybe even pathologies that are poorly recognized at this time. So I think that the, the, the, I think that oversimplification to think of Parkinson's disease as purely a snuclein problem is probably going to be something that we learn about as we investigate the, I, you know, really focus on the biologic underpinnings of the disorder.
And then I'm also interested therapeutically in treating patients with the dopaminergic therapies more effectively and form pumps. And I also think that the surgical treatments for Parkinson's disease, which we haven't talked about. yet, are really important. Both the high frequency focused ultrasound, which I think we're going to see, and more broad utilization in more patients and more centers, and probably new targets.
I also think there's a lot of opportunities for DBS looking at new targets for patients. patients with Parkinsonian disorders to address gait, for example, more effectively. And also potential. The potential we're beginning to see for smarter devices that incorporate AI to modulate the DBS signal to better treat patients over the course of the day.
[00:08:03] Dr. Sara Schaefer:
Great. Those are all really exciting things that I hope come to fruition. I'm sure they will. Thanks for talking to us today.
[00:08:12] Dr. Andrew Siderowf: You're welcome. Thanks for inviting me.