Instant Genius - The latest breakthroughs in Parkinson’s research

Episode Date: August 13, 2026

Parkinson’s disease currently affects more than 160,000 people in the UK. It’s a complex, progressive condition that typically develops slowly over many years and causes issues with movement, balance, and quality of life, and currently has no known cure. In this episode, we’re joined by Prof David Dexter, director of research at Parkinson’s UK, to talk about the latest exciting developments in our knowledge of the disease’s progression and look forward to some cutting-edge treatments that may be available in the near future. He tells us how the different types of Parkinson’s disease affect the brain, talks us through the latest thinking on some potential causes of the condition, and shares some of the latest breakthroughs coming out of Parkinson’s labs around the world. Take your curiosity further with a subscription to BBC Science Focus magazine. Every issue is packed with fascinating insights into the science behind everyday life, the latest breakthroughs and expert analysis, delivered straight to your door. Receive an extra £5 when you subscribe using the code SF5OFF, (minimum spend £20, see full terms and conditions on our website). https://www.ourmediashop.com/bbc-science-focus-magazine-pod30 Learn more about your ad choices. Visit podcastchoices.com/adchoices

Hello and welcome to Instant Genius, a bite-size master class in podcast form. Every Monday and Friday you'll hear world-leading scientists and experts talking about the most fascinating ideas in science and technology today. I'm Jason Goodyear, commissioning editor, a BBC science focus. Parkinson's disease currently affects more than 160,000 people in the UK. It's a complex, progressive condition that typically develops slowly over many years, and causes issues with movement, balance and quality of life. Currently, there is no known cure.

In this episode, we're joined by Professor David Dexter, Director of Research of Parkinson's UK, to talk about the latest exciting developments in our knowledge of the disease's progression and look forward to some cutting-edge treatment that may be available in the near future. He tells us how the different types of Parkinson's disease affects the brain,

talks us through the latest thinking on some of the potential causes of the condition and shares some of the latest breakthroughs coming out of Parkinson's labs around the world. Welcome to the podcast. Thanks so much for joining us. Hello there. Thanks very much for having me. Oh, you're very welcome. So today we're talking all about Parkinson's disease. So, you know, as most people listening will know, Parkinson's disease is the condition of the brain. So first off, what's happening in the brain of somebody who is suffering from Parkinson's disease? Parkinson's is a progressive neurodegenerative condition.

So it affects about 166,000 people in the UK. So what's happening in the brain, there is a protein which misfolds and starts clogging up the neurons in the brain. And it progressively affects a number of neuronal pathways in the brain. The main one that is associated with Parkinson's is the one that controls our movement. And this is what's called the Nyga striatal system. So that allows us to initiate control and terminate movement. And this is why you see the main movement symptoms of Parkinson's.

So how about some other symptoms? You mentioned there the movement issue. Are there other symptoms associated with it? Yeah. So, you know, the classical definition clinically is a slowness of movement, rigidity in the limbs. 40% of people actually have a tremor. But there are 40 other symptoms of Parkinson's. concerns. So ranging from symptoms that you would see in the periphery, like constipation,

problems with regulating your blood pressure, sleep problems, anxiety, depression, cognitive decline, and even dementia in some individuals. So it is a real complex picture there. So based on that then, is it a single disease or are they multiple different types? There's growing sort of evidence that would indicate that there are two main types of Parkinson's. There's one which is called body first Parkinson's and another one which is called brain first Parkinson's. So the hypothesis is that the body first actually starts in the periphery, perhaps in the gut or even in the kidney there's some indications now. And then it causes the bad protein, you know, which is in the nerve endings to misfold. And then it goes up the vagus nerve. into the brain and then start spreading across the brain.

So the other one is what we call brain first. And this might be something in the environment, which we actually breathe in, and it causes the bad protein to misfold in the olfactory bulb. And then that's intimately connected with the brain. So it starts spreading the misfolded protein across the brain. So that's the hypothesis that's been proposed at the moment. So as you said earlier, the disease is progressive. So are there any kind of early warning signs that we can look out for?

Yeah, so Parkinson's UK set up a project called PRED, and that basically does what it says on the tin. So we've recruited 15,500 healthy individuals between the ages of 15 and 70. So we've been looking for these early indicators. And as I say, you know, with 40% of people having what's called body, first Parkinson's. So constipation, you know, sleep problems, anxiety, depression, come in before you actually see the motor symptoms, the movement problems in Parkinson's. So what we're trying to do is actually see whether we can develop an algorithm that will actually spot people who are on the way to showing the motor symptoms of Parkinson's, the movement problems. So you said that

the ages of 50 and 70. So does it typically occur in the older members of the population? That's right. Age is one of the biggest risk factors. And as we're becoming, you know, unfortunately, the sort of the life expectancy in the UK is platoed out. But as life expectancy in the UK, you know, in previous decades was increasing, the incidence of Parkinson's was increasing as well.

So in more developing countries around the world where life expectancy is increasing and they're becoming older, more and more cases of Parkinson's are actually coming to light there. Yeah. So are there any other causes associated with the development of Parkinson's other than aging? As I say, because the brain first, which is potentially environmental factors, you know, a number of environmental factors have been proposed. You know, one of them is particulates, which are the small fragments of exhaust fumes and fattery particulates that's been. Some people have also proposed that certain chemicals or even pesticides can contribute there. And body first Parkinson's alterations in your gut flora, they become more pro-inflammatory in nature. and this inflammation in the gut causes that bad protein to misfold and then transfers up the vagus nerve into the brain.

So how about genetics then? You know, is there a genetic component to the disease? Yes, there is, yeah. So probably about 10 to 12% of people diagnose actually carry a gene mutation. And these have been quite well studied. But, you know, there's probably about 8 or 10 of these gene mutations. so they're quite rare in themselves,

but it's actually given us quite a lot of information about the mechanisms about why the cells are actually dying in the brain. But also there's probably some underlying genetic risk there. You know, it's like not everybody, not every woman develops breast cancer. You know, they may carry risk genes. And we think that, you know, we'll be able to identify some of the risk genes that would indicate that some people develop Parkinson's and other people don't. So are there any kind of lifestyle interventions or measures that we can take to reduce our risk of developing Parkinson's?

Well, exercise has actually been clinically shown to slow Parkinson's progression and also exercise is being linked to a decrease of dementia. So it's looking like exercise is a protective factor against different neurological conditions. So we think that, you know, if you exercise regularly, also with your diet. So diet has again been shown to affect the progression of Parkinson's. So moving more towards the Mediterranean diet, you know, reducing the amount of red meat, eating more fish, multiple different food sources in your balanced diet over the week. So probably, you know, in people that do have more of a meditrain diet and do exercise, you know, they could be protective factors against developing Parkinson's.

So say somebody is starting to display symptoms and they think, oh, you know, this looks, there's something going on here. what happens during the diagnosis process? Yeah, so most people will go to see a GP or they'll go and see a physiotherapist because they've got a frozen shoulder or they might be dragging one of their feet a little bit. So then you'll get a referral to a clinical neurologist or a geriatrician and they will do some assessments of your movement capabilities. You know, they'll get people to walk up and down, corridor watching their movement.

They'll test the rigidity. Is there any rigidity when they try and move their limbs? You know, they'll do various different tests to look at their movement. And also because 40% of people with Parkinson's also have a tremor, so that would also be part of the clinical assessment. So often just to confirm that it's Parkinson's, because there are some neurological disorders that show similar diagnostic indicators

that often a brain scan will be recommended as well. One of the classical ones is that it's called a DAT scan, but this looks at the number of dopamine-producing terminals that are in a certain area of the brain that controls movement. And in reduction in that signal, strongly suggests that somebody has Parkinson's. Right. So how about something like a blood test, you know, are we any closer to developing a blood test to help with the diagnosis? So not at the moment. It's just a clinical diagnosis, but even that is not 100% accurate.

So currently in research, there is a test that's done on the cerebral spinal fluid. So they do a spinal tap. So they actually take a sample of the fluid around the spine. And that bad protein that I said is in the brain, but also it'll be in the fluid surrounding the brain. And what they'll do is what's called an alpha-sinucline seeding assay. So if you put a little sample of the cerebral spinal fluid containing the bad protein into a solution,

into a solution containing the normal protein and you keep shaking it, eventually it will cause the misfolding of the normal alpha-nootling that is in the solution. And that's what's called. So it's almost like it's called a seeding assays. So basically the bad protein acts as a template for the normal protein to start misfolding.

So that, if you couple it with a simple smell test, both of those tests are now almost, 97% diagnostic for somebody that has Parkinson's. So obviously, a spinal tap to get some fluid out from around your spine is not the most desirable. So we've invested people at University College London to try and develop a blood test. And they've been using AI to identify unique patma proteins that is in the blood. And so we're seeing whether that can actually be converted into a diagnostic test that could be rolled out into the NHS. So say, unfortunately, somebody has received a positive diagnosis.

What happens next? You know, what are some of the current treatments? Yeah, so I think it depends on the person's lifestyle. So if they're young, if they're still working, and the level of disability with their, movement actually impinges on their ability to, you know, lead a good quality of life and carry on working. You know, some people may go on to treatment straight away or other people, you know, decide to wait a little bit while until their symptoms progress to a stage. But most of the treatments focus on replacing the lost dopamine that's in the brain.

So this is either using a precursor. So this is a drug called L-dopa. So you take this drug, it crosses the blood-brain barrier, gets into the brain, and then goes into the nerve endings and is converted to dopamine. And then the nerve endings release this chemical messenger called dopamine, and then it helps you facilitate your movement. The alternative approach is what's called a dopamine agonist. So this is something that mimics dopamine directly,

and so it'll act directly on the dopamine receptors and facilitate movement. So most of these drugs actually, you know, they all just tackle the motor symptoms of the condition, but they don't control the non-motor symptoms. So let's have a look at some of the, you know, some of the exciting research that's going on currently. So I've had a look and I picked out of it a few things that seem promising. So the first one was stem cell therapies. You know, what can we say about that? Stem cell therapies are actually, you know,

going through fairly advanced status of clinical trials at the moment. Some of them are in phase three studies. There's three or four different clinical studies now happening across the world. So stem cells have been talked about for many, many years. So originally they were trialing fetal transplants where they took the bit of the brain from a fetus that would normally develop into these dopamine producing cells and then transplant those into people with Parkinson's. Whilst these had positive effects, you know, you've got the ethical issues of using

aborted fetuses there. So then, you know, over the last two or three decades, you know, we've, you know, identified stem cells and now, you know, you can even, you know, you can even take a punch of skin from somebody and actually engineer these cells so they, you know, you can reprogram them and you can reprogram these stem cells into dopamine producing cells. And really what's changed, you know, revolutionized it, is that you can now produce these stem cells in large enough quantities, but also in clinical grade so that you can safely transplant them into somebody's brain. So the early studies which have reported in phase two of clinical studies,

you know, where you're actually seeing that these are safe, but they're also starting to gradually grow and implant themselves into the persons with Parkinson's brain, and it's showing that it has some clinical benefit. So it takes a while for these cells to integrate and develop into the brain as a whole and start producing their own dopamine. So it's not an overnight treatment.

This takes 12, 18 months before you start to see any benefits. But now these are now moving into large clinical studies, you know, with the view that become one of the surgical options for somebody with Parkinson's. But again, you know, these cells are just producing dopamine in the brain. You're just correcting the loss of one pathway. So it's treating the sort of motor symptoms, but it won't treat any of the non-motor symptoms of Parkinson's. So how about another potential avenue of investigation then through the use of gene therapies?

Yeah, gene therapies are really, you know, coming to the forefront, you know, with the recent news about Huntington's, that gene therapy there, you know, was actually, you know, to decrease the level of the Huntington protein, which causes the condition. and they were seeing positive clinical symptoms there, you know, that is actually stimulated a drive, you know, with biotex, academic groups, to actually start looking more seriously at gene therapies. So there are quite a few gene therapies, you know, which are in development. But with the Huntington's one,

you've got the challenges of actually getting these gene therapies to the site of action in the brain. And so often, you know, these are, having to be developed intrithically and that is actually administered into the spine spinal fluid itself and eventually they'll end up in the brain and start doing their good work. There is another gene therapy trial which is starting. So Parkinson's UK a number of years ago funded a trial with a growth factor called GDNF. That's glial derived neurotrophic factor but it is a huge molecule It's too big to cross what's called the blood-brain barrier.

And this normally stops drugs and things and toxins going across into the brain. And so this growth factor had to be delivered. You know, they implanted tubes, delivery tubes into the brain area. And it was delivered by a pump every month. And some of those individuals receiving the therapy, you saw positive effects. So the idea was that rather than putting tubes into people, head, can we actually deliver GDNF through another route? And there is another study that's in phase two at the moment where they're using a gene therapy. And so basically you're injecting

a viral vector and this will instruct other cells in the area to produce GDNF. And it's hoped that you know, that will actually trigger the regrowth of doponogenurons, you know, within that particular brain area. So how about another potential approach using deep brain stimulation? Is that showing any promise? Yes, deep brain stimulation has been around now for quite a while and it is really quite transformative. So Parkinson's UK actually funded the Pivotor study in the UK which really opened up its use not only in the UK but also worldwide. So DBS, I've got to describe this, that when you lose your dopamine, it takes the handbrake off other neuronal pathways, they become overactive. So DBS sends electrical signals and it dampens down those overactive pathways, the block.

You know, when you're thinking about picking up your cup of coffee in the morning, that's just part of it. You know, your dopamine pathways then allow you to facilitate that movement. But since there's no dopamine there, these other pathways are overactive and they block that signal transmitting down to your arms to pick up a cup of coffee. Whereas the electrical stimulations in DBS, you know, dampen down those overactive pathways. So it's much easier to think about initiating and controlling movement. So currently, DBS is mainly used as an end stage sort of therapy. You know, when current therapies are seen not to be working, they get lots of what we call off periods.

And so an on is when your drugs are working and it's allowing you to move properly. Off is when they suddenly lose effect and the person is rooted to the spot, they can't move. So also there's a side effect of current medication called dysgynesias. So this is where the dopamine signaling in the brain is becoming, you know, overactive. So they get these abnormal movements. And so for people experiencing these off periods or dyskinesias, DBS can be a life-altering surgical intervention. And even that, you know, that has been going, you know, quite a number of years. And that has also had a bit of, how can I say, a bit of a change in the way it's done. So in traditional DBS, the stimulator is all. And the stimulator is

on all the time. But if you're sitting in the chair reading a book or if you're asleep in bed, you don't need the stimulator on. So the latest advance is what we call adaptive DBS. So it picks up when you want to move and then it will actually fire up the stimulator and then allow, it will facilitate your movement. And so it allows for a better control of movement. So adaptive dBS, you know, is now coming more into more general use rather than the traditional DBS. But, you know, having stimulators is, and showing the effectiveness in Parkinson's, is opening up a new avenue of research about can we use external forms of stimulation to control movement as well.

There's ultrasounds, yeah, there's all sorts of different ways of, you know, stimulating different brain areas without necessarily how. having to drill holes in people's heads and implanting electrodes. So there's a new avenue of research taking place about using external stimulation as well. Yeah, so by way of summary, then, there's an awful lot of research, promising research going on. You mentioned phase two and even phase three trials that are ongoing. So how promising does the picture look for the next, let's say, five or ten years? Yeah, I think it's on the other side of research, we have much greater understanding about why the brain cells are dying. So we've identified a number of our

processes. I've already talked about the bad protein, alpha-seneutland, which is involved in Parkinson's. So also the mitochondria, which are like your batteries inside the cell, you know, they provide the energy. There's plenty of research showing that they're actually defective and not producing enough energy. Without energy, the brain cells die. Also, there is. an inflammatory process within the brain. And so now we've got these processes that we've identified. Academics, Biotex, farmer, are all directing new drug therapies to target some of those pathways.

So currently there are six drugs in phase three testing. So just to explain a little bit more about that. So phase one testing is all about safety. Clinical trials are all about safety testing. So phase one is in healthy, volunteers. Phase 1B will actually go into small numbers of people with Parkinson's to prove that drug is safe, not going to cause any adverse side effects. So phase two also looks at safety, but also looks to see, you know, is it having any effect on somebody's Parkinson's, whether it

modifies symptoms or slows progression? And then if it's successful in phase two, it moves into these much larger clinical studies that run over a number of years. And so we've got six drugs in phase three. So it's, you know, hopeful, you know, within the next five years, we'll probably identify some of the first drugs that will actually slow Parkinson's progression. Thank you for listening to this episode of Instant Genius, brought to you from the team behind BBC Science Focus. That was Professor David Dexter. If you liked what you just heard, then please do consider subscribing to Instant Genius on your preferred podcast platform. If you'd like to see our guests and hosts and person, then why not check out our YouTube channel at ScienceFocus.

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