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[00:00:41] Prof. Bas Bloem: I explained to the audience that Parkinson's disease is the world's fast growing neurological condition, it doubled in the last 20 years. It is expected to double again in the next 20 years. And while this is worrisome enough by its own, I explained why I think this growth is, at [00:01:00] least to an extent, if not to a large extent, driven by environmental toxins, making Parkinson's potentially a preventable disease.
The focused workshop here was exciting. It was wonderful. It was a glimpse into the future, and we were talking exciting new disease modifying treatments, which if applied to an at risk population, who is still free from, you know, a clinical diagnosis, we could eventually postpone or perhaps even prevent Parkinson's disease.
At the same time, there were fairly hefty debates whether this is the road forward, because it will be costly, and we don't have those treatments. And I argued that at least in addition to those secondary prevention strategies, we should focus also on primary prevention, really trying to stop the growth of Parkinson's from happening, and we can do that by tackling environmental risk factors.
[00:01:53] Prof. Tiago Outeiro: It was very eye opening. I think we need to think about it in this way because it's a big problem. But when [00:02:00] we think about pandemics, of course, we think about the numbers there were, of course mind boggling because the whole world was affected. Here, although the numbers are large, people may think, okay, well, this is not really a pandemic.
So what is the strong argument to convince people that this is a serious problem? I think we don't need to convince us. We are convinced that we need to go out there and convince people that they need to change behavior. So how can we convince them?
[00:02:25] Prof. Bas Bloem: Well, we use the word pandemic on purpose. It's a nice alliteration, Parkinson's pandemic. But we use it to open people's eyes. The definition of a pandemic is a disease that is occurring worldwide, and we can tick that box, that's growing fast, and we can tick that box, that is sparing no one, men, women, young, old.
Make no mistake, in the Netherlands, one in three people is under the age of 65 when they develop Parkinson's disease. We have special programs for young onset Parkinson's. So Parkinson's affects everyone, and a [00:03:00] pandemic leads to debilitating symptoms, and Parkinson's is one of the most terrible things that can happen to mankind.
So except for an infectious cause, Parkinson's disease fulfills all the criteria of a pandemic. And I think Parkinson's deserves more attention. It deserves more funding to develop better care for affected individuals, to slow down disease progression, to hopefully find a cure, and at the same time, try to stop the growth from happening.
[00:03:27] Prof. Tiago Outeiro: Makes sense. And the workshop, as you know very well, was on biomarkers and diagnostics. So how do you see the current state of affairs and where we are with the latest developments on biomarkers and how this may help change things also at that level, because people now know that there may be a test that they can do and that may give them some information.
So how can we think about this so that people know that this is not a solution, but it [00:04:00] may be some piece of information that will, give them some sense of whether they are at risk or not, at least in the future, as the markers improve.
[00:04:07] Prof. Bas Bloem: Yeah. So what we discussed, and I think Angelo Antonini did this beautifully in his talk,
is that we still diagnose Parkinson's much the way Jean Marie Charcot diagnosed Parkinson's with his bare hands, listening to patients and doing a neurological exam. That's on the one hand the beauty of our job as movement disorder specialists. We love our job. But at the same time, we know that this is a late event.
By the time we diagnose Parkinson's, 60 to 70 percent of dopaminergic neurons are lost. We know from the work of Per Borghammer that the disease is elsewhere in the body, it's elsewhere in the brain, depending on the specific phenotype of Parkinson's, but it's a widespread disease.
And all attempts to slow the progression have so far failed. Now it could be that the hypotheses were wrong. That's not something we hear a lot, but it could be that the hypotheses are wrong. It could be that a single [00:05:00] target treatment is not enough, that we need cocktails of treatment targeting multiple mechanisms.
Or it could be that we target the disease too late. So what was exciting is that we now have avenues of diagnosing Parkinson's earlier, which opens up the door for testing new interventions, whether this be pharmacological or non pharmacological, to slow down the progression in an earlier disease stage.
Importantly, this is all research. And I think there are concerns in our society. And I expressed those concerns in an editorial in Lancet Neurology that this will spill over to daily clinical care. I think this is an important development and I encourage it. I'm happy with it, but it's for research purposes and research purposes only.
And what is happening is that apparently people can now buy an alpha synuclein and then go to their doctor and say, and now what? And I think that's bad medicine. It's bad medicine because we don't know the prognosis, we don't [00:06:00] know whether a positive alpha silicon test will translate into symptoms.
And we have nothing to offer these people, except for what we can tell the general population, which is exercise, eat healthy, stay optimistic, and avoid exposure to pesticides and other toxic chemicals. So, yes, this is an exciting time. We are going to see trials in prodromal Parkinson's, but I think we should steer away from letting this slip into daily care.
And this has happened in the Alzheimer's field and not to their benefit, at least in my opinion.
[00:06:31] Prof. Tiago Outeiro: Of course, this is a very important issue. And that was the idea when our paper was written, at least that this was proposed for research purposes. And of course it's very difficult. things. Once they are out there, people will interpret them and think that they can go and use it.
But I mean, we face the same or a similar situation with genetic testing. Any person can, can go and do a genetic test. This is also, I think just one additional factor that we need to consider and that should [00:07:00] not be done out of context that should not be done. You know, misinterpret what they have in front of them.
But yeah, that's, that's important, definitely it's a discussion that needs to continue. You have been talking a lot about exercise and how this can really have an impact on changing disease progression. So what can we do to, to convey this message seriously and forcefully to the general public.
What can the MDS community that listens to our podcast do on their own to pass the message?
[00:07:31] Prof. Bas Bloem: So first of all it is exciting to see the pharmacological developments, all these different types of approaches targeting elements of the pathophysiology of Parkinson's. My concern is that tackling just one of those elements per trial may not be sufficient.
Ultimately, the pathophysiology is the sum of inflammation, alpha synuclein accumulation, vascular contributions, etc., etc. So just like we are preventing strokes with [00:08:00] antihypertensives, cholesterol treatment, antiplatelets, we use cocktails, we may need cocktails of different drugs. What I like about non pharmacological interventions is that they are probably more agnostic to the precise disease making mechanism.
We know that exercise drives, for example, neuroplasticity in the brain. We've shown this in imaging studies. We know that exercising muscles release irisin, and irisin drives plasticity in the brain. There are cool studies to show that exercise releases clostridine, which is an anti inflammatory protein.
So exercise has the potential to tackle multiple mechanisms at the same time. And we know that there are two studies to show that exercise slows down clinical disease progression, which is not disease modification yet in clinically manifest Parkinson's. And there's a range of studies that show that people who exercise a lot during life have a lower risk of developing Parkinson's.
That's still not enough to conclude that exercise is a disease modifier, but [00:09:00] it's close. There's animal work to support it, there's the imaging work. So compared to an antibody against alpha synuclein, if I had to put my money on, I would put it on exercise. This is why my group, along with colleagues in England and the United States, is now doing the slow speed study, which is the one of the world's first completely remote studies.
Nobody comes to the hospital. Where we randomize people across a lot of extra exercise versus a little bit of extra exercise. And in answer to your question, we work with the gaming industry to really exploit human weaknesses. We give people rewards for reaching their targets, which in the intervention arm is a high level and in the control arm is a low level, but they receive the same awards.
And by using gamification elements and reward mechanisms, we hope to push compliance. It's a sort of a Pokemon Go for the elderly. We've already tested it in the stepwise study, which is using the same gamified app on the phone in people with manifest [00:10:00] Parkinson's. There are already 300 patients in the study and compliance is excellent.
So it works. I think gamification helps, but what helps mostly I think is deep learning. So in my clinical practice, I talk about irising. I talk about clustering. I show them the images of plasticity of after exercise, new functional connectivity between the basal ganglia and the cortex.
Because ultimately, if people understand the why, they will do the how and what. So we tend to focus on the what, but we forget the why. So deeply invest in why and deep learning, to our society, through lectures, through our education programs, and to the wider audience remains critical.
[00:10:39] Prof. Tiago Outeiro: I think that's great advice. I know you exercise, I exercise, so let's hope all our
listeners
[00:10:44] Prof. Bas Bloem: Practice what you preach.
[00:10:45] Prof. Tiago Outeiro: Yeah, exactly. We want to promote exercise as well. Yeah. Bas, thank you so much. Anything else you would
like to add?
[00:10:51] Prof. Bas Bloem: No, maybe that in addition we talked about exercise, the next big kid on the block is diet. Diet is very difficult.
We are embarking on the first dietary [00:11:00] intervention studies. We know that the Mediterranean diet is associated with a lower risk of developing Parkinson's. Two studies show that the Mediterranean diet leads to lower mortality after diagnosis. Doesn't prove anything. Pesticides reach the food chain.
What can we do with a biological diet that slow down Parkinson's? So, just to mention that there's a whole world to be won. In addition to exercise and the many pharmacological interventions. So we are living in exciting times Tiago.
[00:11:27] Prof. Tiago Outeiro: Wonderful. I like positive messages. Thank you so much. It was the pleasure of us.
We've just interviewed Bas Bloom on the occasion of the MDS-ES workshop on diagnostic and progression biomarkers in Parkinson's disease and atypical Parkinsonism in Padua. So I thank you all for listening, and I invite you to join us in our upcoming podcasts.
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