So, hi, Jose. How are you enjoying the MDS Congress?
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[00:00:31] Prof. Obeso: Well this is just another highly successful meeting. In this instance, obviously, everything is influenced by the very fact that they have been no other in-person meetings for three years, which may give perhaps a little bit more emotional and personal weight. So I think that the first feature this year, meeting and wanting to spend more time speaking and saluting people than to the actual core of any normal meeting. But this is where we are currently. The meeting is broad as is always been in the last many years, and clearly representing the evolution of this area of neurology of movement disorder.
Movement disorders has evolved in such a way that is now a really very wide area of knowledge, study and development. I think the meeting captures that variety. Retrospectively, perhaps 30 years ago, 25 years ago, the meeting was less wide and was more narrow because developments were more focused.
Nevertheless, to be more concrete, I think we can take today's presidential lectures as an example of how we feel is evolving. Today we had Professor Kailash Bhatia speaking about genetic movement disorders and the role of phenotyping. Currently there are an enormous variety of movement disorders, and with plus minus other clinical presentations, or the clinical manifestations, which have a genetic basis. And that is expanding more and more with getting more and more complicated. And Bhatia's point is that really featuring, and well defining the clinical presentation is still critically important, and he that it will be important for a long time, at least.
I would even be stronger, I think. I think that genetics will only be confused and will be disturbed in its development if clinical evaluation is not correct. And we are seeing that, in fact. In fact, this is a threat, that as less emphasis is made in the clinical details and the very roots of of this specialty, this may actually lead to more confusion rather than improvement.
Having said that, it is obvious that the more one understands the molecular basis of a disease, the better one can typify, subtypify — that that was the second lecture , Professor Hattori — indicating how a mutation — he of course devoted most of his life to Parkinson's and of the mechanisms associated. But clearly, I think this is a very interesting message: clearly a mutation by itself, does not explain if this is Parkinson's disease to begin with, because the mutation is universal in the nervous system or in the body. And those patients, for instance, the very good example of patients with Parkinson's actually have a very, quite specific and neuronal loss for a long time. And Hattori was actually wondering, how can it be? This is so slowly progressive and relatively limited clinically when for such a mutation, which is so important on the mitochondrial level and the acting synapses, synuclein, et cetera. So clearly one is, I think still needs to be very accurate in defining what the patient have.
And I think for the time-being ... mid future, not near future, mid future, it will be a tremendous error to put all the trust and hope in the genetic analysis. Because, after all we know that imaging has not resolved. Neurology has helped a lot, but it still has not resolved.
Then is this matter of therapy. Therapy for Parkinson's disease, which is abundant. There's nothing new in that regard because every year is enormous abundance of therapies. Most of which, if not all, are symptomatic.
So this is my next clear message: the real unmet need for Parkinson's is to tackle and to approach the process, not just the clinical manifestations, which now are very described or very overtly described. Not only the typical motor feature models, the whole plethora of clinical manifestation that symptoms are more or less treatable, et cetera.
Lot to improve. But nevertheless, the real thing here is to approach neurodegeneration of the disease. And on that regard, there is less, although clearly a major effort.
But of course, imaging is the real highlight of neurology, neuroscience, and neurodegeneration in particular, and the synuclein. Upcoming there is data about PET imaging or synuclein uptake. I think that is this year's breakthrough, if really confirmed and made available.
It's also important to point out what is missing and, and there are a few things that I sense are being left out. Because after all, what medicine and research and academic medicine does is influenced by fashion and is influenced by opportunities.
And then for instance, we already have had quite a few meetings where other movement disorders, like myoclonus, are practically absent. Tourette, very little about tics and Tourette. Pathophysiology, as used to be in humans is also very limited. So it's a shift of course, 20, 25 years ago, there was nothing about imaging. There was not PET, et cetera. So it's a balance. Something die out . But, I do wonder why there is so little advanced on myoclonus. So this, I, I leave it there.
[00:07:24] Prof. Outeiro: Your broad view of the field for such a long time is really an advantage because you allow us to integrate what has been there for a while, what's new, what we need to do next. So I think you touched on very important points, and we are still on day two of the Congress, so of course there's still much more to come. But I agree, the Presidential Lectures today were very good in telling us that we need the clinical diagnosis. And we need, of course the new tools, the genetics, the mechanisms. And so I think that's very important. And we need these applied not only to Parkinson's, but to the other movement disorders, as you just pointed out.
So you will be talking on Sunday about the highlights of the year in Parkinsonism. Is there something else you would like to add regarding what you will be mentioning in your presentation?
[00:08:14] Prof. Obeso: Certainly, certainly. I'm going to make a few general comments, some broad ideas about what is happening last year in PD Parkinson's.
And then I'm going to concentrate in vulnerability and understanding that if one takes Parkinson's disease early in the evolution, in relatively non very aged people, let's say people around 60, which is a medium age of onset for most studies, but not people who are 77 or 82. So PD typically there is quite restricted to, is mainly clinically expressed by motor focal problems and non-motor manifestations occurs much later. But for me and conceptually and instrument, the early PD, if it's 50, better than 60 represents the essence of the disease. And then whatever else associated with aging is an evolution of the principle phenomen. So, taking a younger group of people with PD, they are very focal. Extremely, typically limited to one upper limb and this one, etc. And in those people the neuronal loss, the synaptic loss, is quite limited actually to the nigra striatal system. It's not completely, one would argue, 'this is not true.' And it's not true. It's just that that by and large, this is the principle pathology alteration. And so why those cells in the ventrilateral nigra compacta cells projection to the posterior putamen , why those terminals are especially vulnerable. Probably that had started to occur in those particular patients, 15 years earlier, 10 years earlier, at least clearly we know it's a very slow phenomenon. So why somebody who is 45 is already having a pathological process, which is already damaging, although unnoticed, but it's already damaging. So they have to be very venerable.
And because we understand the universal mutation actually is also affected by venerability because those neurons are precisely much more affected that anywhere else. It makes a wonderful scenario. So I have been revising and reviewing articles related with phenotyping at the molecular genetical level, the ventral lateral substantial niagra, the topography of the cells, their projection, and also the difference of the is fascinating. Of course, most of these studies are done in rodents, and that is a limitation.
But I think at this very basic level, it's probably true, but we need to remember that the rodents never has Parkinson's diseases spontaneously, not even monkey has Parkinson's diseases spontaneously. So obviously those features that are being now defined like the number of enzymes that are expressed, the connectivity, etc., Those features by themselves are necessary, but not enough to explain the, degeneration.
So I'll be revising that mainly, and then showing some more recent studies, showing also what is the very early changes that occur at the cortical level, which is a kind of little new look.
So we are going to start looking at PD not only from bottom up but also top down.
[00:12:04] Prof. Outeiro: Great. I'm looking forward to listening to you. And I think the message is really that we still need a lot of research to be done . So Jose, thank you so much for your time. It's been a pleasure having this meeting with you on the podcast.
We've interviewed professor Jose Obeso and discussed the highlights of the MDS Congress in basic science. So thank you all for listening and join us in our upcoming podcasts.