The Furries And The Sower Of Seed

PODO You're listening to Movers and Shakers, a podcast about living with Parkinson's. The show is sponsored by Cure Parkinson's, whose urgent and only goal is to find a cure, and funded by BoardWave, a networking community for technology leaders and a passionate supporter of Cure Parkinson's. For more details on the charity's progress around research and its fundraising, please visit cureparkonsons.org.uk. [Music] Hello and welcome to another episode of Movers and Shakers. I'm Rory Ketlin Jones. We're not in the pub this week. We're online for another in our summer series of parking profiles. Getting a day when both we and our subject, one of the busiest men in Parkinson's research, could be in the same place at the same time proved impossible. So we've tracked Roger Barker for it is he, down to his Cambridge office. But first let's see who's dragged themselves to their computer on his hot summer day for the call. I'm Paul Mayharker and I have literally just dragged myself to my computer. I'm Mark Modell, I'm in the garden, so I'm not some cool. And I'm Nicholas Mosten, fresh off the golf course where I'm pleased to say I got my first ever eagle. Or are? Somehow when you that that was coming. Now to our guest Roger Barker is professor of clinical neuroscience at the University of Cambridge and consultant neurologist at Addenbrook's Hospital Cambridge. If that sounds to you like a typical ivory tower academic incapable of engaging in the real world with real people, well nothing could be further from the truth. Roger is the most approachable of men and can explain his groundbreaking work on seeking to use fetal and stem cell transplants to treat Parkinson's in language we can all understand. It was also head honcho, I think that's the title for the world Parkinson's Congress meeting in Phoenix, Arizona back in May. And we're eager to learn how he thought that event three years in the planning turned out. Roger, welcome to Movers and Shakers. Well, thank you very much. Thank you for having me back. Right. Well, we're each going to take charge of a particular area of questioning and Mark, you go first. Yeah, so we want to find out how you become in your office. So in any one of those kids who always always clear that they're going to become adoption professor, what was your background? Yeah, so I sort of decided to do medicine when I was about 15 or 16 basically because my friends were going to do those age levels that and so I thought that sounded quite good. And that's essentially the only decision I've made in my life in terms of my professional career to become a doctor at the age of 15 and 16. And becoming a neurologist, that really happened when I was an undergraduate. There was an amazing chap in Oxford called Tom Powell, who was one of the great neuro anatomists of the late 20th century. And he made neurology seem very or neuroscience, very easy. So he gave his lecture, this is a piece of cake. Can't see why people find it difficult. Then I opened the book and found it was slightly more difficult than I imagined. But actually then at that point, so my second year as an undergraduate became slightly obsessed with the brain. And then my only deviations for that was I got quite interested in tropical medicine when I went as a medical student, then I went to a tropical country and got a tropical disease. So I went off that idea because I didn't realize you could actually catch these things. And then I quite liked intensive care unit, but I thought that was quite straightforward after a few weeks and months. And they weren't really taught you very much in terms of the patient interaction. So after that, it was just neurology after you do all of your training. And I never regretted it. And to this day, I love my job. And we just go back a bit before all these decisions happen. Were you a swat at school? Where were you brought up? Were you one of the people who always got their homework in on time or what? Yeah, so at school, it was a sort of curious life, I suppose. I certainly at school was not regarded as someone who's going to do anything very special. And I was at a very academic school where lots of people went to Oxford and came and did all sorts of very complicated degrees. And then I went to school and I was regarded as a sort of also ran. And I remember after I got my A level result, I went to my career teacher and said I would quite like to do medicine at Oxford. And he just looked to me and said, well, I suppose someone's got to do it there. And I didn't feel particularly inspired or encouraged by those comments. But nevertheless, it's decided that I would press on. And my family art, particularly academic, you know, my mother had to leave school when she was 14 and my father was an interesting character who would very much relate to Donald Trump. And he imagined the sense of how he carried out his life and how he behave. So he at some point already wanted to be a doctor but having failed all his A levels, he then decided on a different career. Since you were very interested in neurology, why do you think other doctors aren't as interested? Why aren't the people crying out to become neurologists? The perception is neurology is very difficult because obviously part of the trick is to listen to people and just still out from what they're telling you where you think the problem is and what the problem is. And then actually being able to put that into some sort of diagnostic test. So can I do something to work out what it is? Certainly when I was growing up, that was harder because it was much less imaging. So when I qualified, MR scanning wasn't actually available CT scanning when I was a junior doctor didn't exist in some hospitals where I worked for any part of the body. So there was a lack of tests and also there was a sort of sense of nihilism. You just sort of went to clinic. You told everyone what they had. You wished them all the best and then often they went and there was very little you could do for it. So in the 1980s when I qualified, I mean basically epilepsy could do something for Parkinson's you could do something for MS you gave a bit of steroid but really it was thought to be a bit sort of depressing and too difficult. Unlitrically medicine you can't catch the disease. Yeah, well I did have some medical school but a bit of a hyperchondriac and he decided to do ox and gyne because he was absolutely convinced he couldn't get anything but he was. If the people he worked with were having. How would you sell the honesty to young doctors now? Well, I think the wonderful thing about neurologist you never know what's going to come through the door. Because it you know there are so many different things that can come listening to the story a lot of it overlaps with psychiatry so it's all it's never boring. I think you know investigations and treatments have come on so much in the years and we can do so much but there's still so much more we can do. And I think it's that which took me into your object. So you've qualified as a neurologist. I qualified as a doctor. You've actually become a neurologist and the great sort of saga of your life what it seems to have been from the outside is this whole adventure with cell replacement which is occupied what the best part of 30 years. Tell us how that got started. Yeah, so it's a series of steps. I got very interested in a bit of the brain called the basal ganglia which are these brain structures deep within the brain which are primarily affected by a number of conditions which Parkinson's is the classic one. And then when I was a junior doctor actually working at Canterbury I read this paper which had been published in the New England Journal about some people in Mexico who tried to repair people's brains in Parkinson's by putting cells in from a thing called the adrenal gland. And it's next to your kidney that produces adrenaline or adrenaline, not much dopamine but they managed to get it to work and I suddenly thought now that my friend is a very interesting concept that we can think about repairing the brain and particularly around Parkinson's. So at that stage I was very interested in the idea of repairing the brain and then I had to finish my medical training before I went off and came to Cambridge to do my PhD. And then I had a period of time I kept coming up with various theories on how things worked and as an aside I used the right letters to journals about my various ideas and I decided that because I lived in a basement flat in London that didn't sound very good so I renamed my basement flat the Institute of theoretical neuroscience. And then I went to the Institute of theoretical neuroscience and I had a period of time I had to finish my research and I had to start the research. I was really interested in the science that I was experiencing and the science that I was experiencing was the scientific and scientific research that I was experiencing. So let's follow by disasters just take us through a bit of that. So the original study was actually in mexico and it was a very bizarre study with the adrenaline in the brain and it sort of it sort of worked but it was very hard to understand how it worked and say about the early part of the 1990s there was a sort of sense that that type of tissue was a bit odd but the replacing the lost dopamine cells and pugs with human fetal tissue which was very controversial because these are cells you have to get from the board of fetuses. There was evidence coming out in the first part of the 1990s that this was producing some very dramatic responses in some patients and so it was really gaining momentum in the 1990s at a time when deep brain stimulation haven't really come in that came in about 92 93. So people have been looking for these better treatments for pugs is to get rid of some of the complications with the medication the on off the disk I use as and the results were looking very encouraging. It's slightly got derailed really at the turn of the century because in the late 90s or the mid to late 90s when Clinton was in the White House he liberated NIH funding or fetal transplant trials in pugs is which had not been allowed by bush senior and those trials which were very premature I would say and had some major methodological problems published in 2001 and 2003 saying it didn't really work. So I really hit the end point it was supposed to there was side effects from it and so the field took this very badly and thought this clearly hasn't worked and by that stage the way your experience and your experiments work to tool. very much more interesting, Dean. things in the lab to better understand how we could promote the survivor of the dopamine cells because even in the 90s it was clearly a problem with getting enough surviving dopamine cells to have an effect. And I think the studies in the states had problems with who they selected, they had problems with the immune therapy, they had problems with the amount of tissue they put in and how long they waited to see the effect. So I think there were positive signals in there, but they hadn't quite optimized it. And as a consequence of those two negative trials and I have no idea whether it was relevant or not, but obviously they're now playing out against the bush junior in the White House. There was a sense that this had come to an end with cell therapies, deep range stimulation was coming through as being a very effective therapy, fantastic videos of how it worked. And so there was a slight sense that it was becoming a sort of historical put note. It was an interesting concept, let's leave it, but clearly intuitively it's a very obvious thing to do. You lose a quarter of a million dopamine cells, why not just put back a new quarter of a million dopamine cells? I mean you don't need to be Einstein to think that that's quite a good idea. The question is how can you do it and can you do it consistently? And it's right back in fashion right now, isn't it? Tell us what's happened in the last few years, but it did. Yeah, so I think the big change came about 15 years ago, 2010, 2011, when people worked out how you could take a human stem cell, so whether it's been embryonic stem cell from a spare embryo from an IVF program or a reprogram skin cell or blood cells, they're called IPS cell, they worked out how you could turn that into a dopamine cell of the type lost in Parkinson's. And those discoveries made in by Marlin Palmer and a team in Sweden and Lorenz student, his team in New York, meant we suddenly have the capacity to now make dopamine cells and lots of them and we could control the manufacturer of them so we could have enough of them, we could engineer them if we needed. So on the background of that, there were other years where people including Junta Kehashi in Japan worked on how you could make embryonic stem cells into dopamine cells of the type you needed to repair the brain Parkinson's, but make them at a level which would be acceptable in the clinics and they have to be have a clinical brain. So by 2018 that had been achieved by many groups, we were a bit later to that. And then over the last 10 years, they have now entered clinical trials. So now there are at least three published trials that our trial will come out to where people have taken human stem cells, turn them into dopamine cells and transplant them into the brains of people with Parkinson's, and they're probably at least another, I would think, 10 or 12 trials ongoing around the world at the moment with these. So this has become a major area of interest and excitement and the problem with all of this is there's always a sense that everything will work perfectly the first time you have a go at it and so there's a lot of hype I would say about the early results and then when they don't quite plan out as you expect, which is what you would expect, then people get very disillusioned very quickly. So in a world that has an attention span that's very short, this sort of plays into that sadly. And so you're, you're sounding quite skeptical that this idea that you've been working on for so long is going to work. Well it will work, I have no doubt it will work because I can't see why it wouldn't work, you know, simply replacing the cells that are lost with replacement younger versions of themselves. We know from the fetal tissue that if you get it to work, it can work incredibly well. So the best result, you know, people 30 years into their Parkinson's, 20 years after a transplant on no medication, normal dopamine levels in their brain and really motor scores that are no different from when they present it 30 years previously. So when it works, it works very well. So we have proved the principle. The problem is we haven't worked out things like dosing, we haven't worked out how to give them, we haven't worked out the optimal way to actually transwant these cells into the optimal person. And so it's very unlikely that the first time you have a go at that, you're going to get it right. And the problem is I would say that the trials that are published to date, including our own, have shown that it can be done safely. There's no problems with the cells growing into tumors or migrating off around the brain. But in no trial, as anyone, safe arm managed to put the brain back to normal around the replacement of the dopamine cells. And that is probably because of the reasons I've said. But if you read some of the editorials and some of the comments, then people would think we're already there and we're not. And if you set up an expectation that you've already solved it and then it proved not to be, it's a huge letdown. And so that's my worry is that people are running slightly ahead of where the data is currently. It seems thinking about what you just said that transplantation is the primary issue, isn't it? Well, it's the sort of mechanics of transplantation. So the problems you need to address are rather present, you know, compared to making dopamine cells, which sounds terribly wacky doing exciting. What we need to work out now is what is the dose because most of the cells you transplant die when you put them in. So you have to work out what is the number of cells you need to put in in order to get sufficient to survive in the place where you were. First of all, human fertilization in that sense. Yeah. And you know, I often say, you know, if you look at heart transplant, people always remember Christian Barnard and our generation do. So he was the first person to transplant a heart. But I mean, the patient lived for about 10 days, I think. So from their bodyguer, it's a point in this exercise because it really didn't make any difference to their life. But it showed you could do it, but you now needed to solve the next problem. And I would say that the trials have demonstrated we could do it. But we now need to build on that to work out. That's the ultimate. Of course, what you've been doing is addressing the this phenomenon of the death of the dopamine producing cells. And the smoking gun is commonly assumed to be this road protein alpha-cynuchin, isn't it? Yeah. That is commonly regarded as the smoking gun. And in Phoenix, a debate was put up, I think, to stimulate interest and for a form of entertainment in which the, you know, the proponents in favor of the theory of the smoking gun argued against those, including yourself, who I think you put yourself up as an art saline, didn't you? You didn't put yourself up as an actual believer in this, but you put up so that both sides of the argument could be put. You know, as we were discussing beforehand, you were like a barrister given a brief. Precisely. Well, I wasn't actually going to do that, but my pain had started on that. So I wish to, I wish to put the case that my, that alpha-cynuchin was not a serial killer. And the only evidence was circumstantial and you have no proof to put him at the scene of the crime. So this was World Parkinson's Congress, yeah, in Phoenix, which happened in May. And this, for me, was the high point of the whole event, this clash. Did you realize that passions would run quite so high? Well, it's an interesting because we've never done these debates before. And subsequently, I have had some pushback. So from some colleagues in various charities, they feel that actually the debate was a bad thing because they argue that it left patients very confused and that was a very bad thing to do. Whereas my view was that actually it's very important that we have these debates in that open that we hear the evidence foreign against. And in this particular debate, no one really wanted to stand up against the argument that alpha-cynuchin is the, which is the keyword, the central player in the pathogenesis of Ponzi, is actually the cause of Parkinson's disease. And I think it's very good as a scientist to argue your case. I would always like to argue against myself. So if I was to have any debate, I would say I would argue take the side of this side, this house believes that cell therapists have no future in public things. So I could argue against myself because I probably know more about it to argue against the arguments, which I would put forward to support it. I think it would be irresponsible not to put both sides of the argument. It would look highly partial and party-prevented. Yeah, sorry. I just understand one tiny thing. Alpha-cynuchin protein, we all have that, but we're talking about the ones that go wrong, aren't we? Yeah, so basically, alpha-cynuchin makes up about 1% of your brain. It's clearly vital for how your brain normally functions. And for reasons that are not clear in people with Parkinson's, this protein misbehaves. It adopts some funny form, then starts to accumulate. And as it accumulates, it then eventually forms its luri bodies and lewy neurites. I understand that. Do pathological studies give us any clues to why the protein goes rogue? Not really, except, well, there's this whole theory that we know once it starts to go rogue, it can then spread around the brain and see pathology as it goes. So this is this idea of protein spread. So the idea would be one set of cells for whatever even develops an abnormal form of alpha-cynuchin. It starts to form problems in that cell. It passes it to another cell and then templates that cells normal outside. You can come abnormal life of one that's infected it. And so it spreads through the brain. A bit coming back to what you're saying about CJD, you know, that's a sort of principle how prime diseases work. But there's the evidence for that is, it's not overwhelming. And so the initiating event what actually goes wrong is very unclear and where it goes wrong is very unclear. Does that mean in this search for a cure that you're all floundering around actually? Unlike, for instance, as far as I can see, multiple sclerosis where there's more understanding of the actual process going on and there's been more success in finding therapies, we're still sort of shooting in the dark. Well, we're looking for a needle in a haystack, can't we? Well, yeah, I guess you could argue either way really. So the thing about MS is it's obviously, as always, we need to have a lot of information. The question is can you just hit information hard enough with the drugs, which actually can stop it? And that's been shown to be the case. But even in MS, if you can stop the information, you still can't stop some of the downstream consequences of it. Now Parkinson's, you could say, well, alpha-cyne is clearly involved, you know, the question is, is it the central player? Is it the only player? And I suspect it's not. But if it is a key player, then if you could target it, regardless of what happens upstream of it, if you stop it, you could slow down the disease. So I think it's a good place to target your therapies. Part of the argument I was putting forward in the debate is in the world of Alzheimer's, as you probably know, there were two proteins, there's amyloid in there now, and a lot of efforts gone into dealing with amyloid over 30 years. And really, the impact has been relatively small. And it's not that that's a bad strategy. It's only a bad strategy if you do it to the exclusion of everything else. And my worry with the world of outside nucleic andpoxies is all the efforts put into trying to target outside nucleic, which is probably reasonable place to stop. You shouldn't be doing it to the exclusion of other therapeutic approaches. And my own view is that actually I think the best way to treat poxies is to target several different pathways, all of which are implicated. So I would target outside nucleic, knock down its production a bit by reducing it through various strategies. I would probably try and give drugs which increase clearance, where you see you get rid of proteins out of cells and I would probably give something that dampens down inflammation and if you do that, that sort of multi-pronged approach, you have a little bit of effect in three areas, three little bit makes quite a big bit and I suspect that will probably be how we can turn the dial on this condition. I was in - each by Rory's interview with Matt Farrer from Phoenix in which he said that he thought there wasn't enough philosophy of science done and too much data collection - do you agree with that? I think there is an element of that. I think there is always this balance between as we get cleverer technologies and collect more and more data that we think we're making progress and we obviously are making progress but the key thing is interpreting the data you've got in front of you. So collecting data isn't itself discovering anything, it's just collecting data and then there's this great belief and I'm a bit of a luddye here, you know, that AI and machine learning will transform what we collect into something which will be helpful and I'm sure it will make a useful contribution but I don't think having us look at it is a bad thing because I think we have to try and fit it into sort of biological principles which which may be an AI but I think you know there's a sort of intuition that you have in people which is not necessarily there so I think there is more data that we're gathering which is helpful but we do sometimes get a bit overwhelmed with it. The point I think was that there wasn't enough focus on the cause of what really causes Parkinson. Yeah well and I agree with that and I was just a lighting science cross Parkinson's meeting last week which is much more about you know what underpins the problems in Parkinson's and it's an incredibly difficult question to answer because I think part of the problem is it's probably not one thing that causes it. It probably begins years before people ever know that they've got a problem so when should you be looking there's a lot of evidence that things in the environment are important but the question is what are those and I remember doing a someone's PhD by over here where they had looked at this big cohort of patients collected in Norfolk about 30 years ago where they collected everything about and their occupation where they lived what they ate and then some of these people going on to get Parkinson's and you sort of look back and you say well actually these people have post-ins they weren't that many but they seem to be a bit more salted peanuts than cashew nuts or something you know and you sort of think well what does that mean I mean you know trying to make any sense of it is extremely difficult so I think trying to tie down what is outside of us are in the environment what we eat it could be triggering it's very difficult and relying on people to tell you it's not as helpful because we all have recall bars you'll remember being locked in a greenhouse with a bunch of pests aside sprayed on your head when you get Parkinson's but you won't remember having flu or gastroenteritis because you think that's not relevant but it may be. Yes what about suppression of symptoms completely that would count as a cure wouldn't it? Yeah so I often say this that you know I think what people fail to realize is how good symptomatic therapies are so in the pre-eldop rearer I mean I don't have the exact figures but I imagine you know if you've got paxies in the forties and fifties you were unlikely to live more than ten years because you were just crying to a hole and so elbow become along doesn't actually affect the underlying pathology but in the community your life expects you with paxies is normal so in that sense you know a symptomatic treatment can have disease modifying effects and you know another example I was think asthma you know an asthma very few people occurred of asthma they have asthma all their life but now they have good treatments for it so they live a normal life. Right, viral drugs for HIV. Well HIV is an interest yeah I quite like HIV is an example because HIV obviously the advantage there is you know what the infecting organism is the HIV virus but what you can have done is they realize that in order to tackle HIV you can't just tackle one part of a pathway you need to tackle various parts of the pathway and by using that combination therapy you can essentially cure people of HIV and that's the model I use for paxies we might not be quite sure what the initiating event is like you know for HIV for infection but you do know bits of the pathway they're important so why not target them? Going back to the debate I wasn't feeling it but unfortunately I missed the debate and I say unfortunately because reading the accounts of it sounds quite extraordinary the passions that are aroused. The way guys met that? Why was it you think? I was a bit surprised if I'm honest I mean debating I think it's a wonderful is a wonderful thing I think the UK does it extremely well I think our parliament well used to have very good debates and probably still does outside of the headline so I think it's it's a bit in our nature I think people do feel very strongly about things and part of the problems in science is that people get very passionate about things which is good but they can be passionate and become a bit of cesset and fail to take on board criticism or they take them personally so I was surprised by how much people worked up about it I was also very surprised by how controversial the controversial session became in itself I have to say so there was a controversy around the controversies which I hadn't really expected to be honest. I just want to say I hadn't been to pay it I hadn't been to Barcelona so I went to Phoenix for the first time for which I'm thank very much to your Parkinson's paying for my costs but I just want to say it was I think one of the best things if not the best thing I've ever done it was absolutely fantastic in terms of knowledge in terms of emotion in terms of friendship in terms of collegiality every time I think about it I almost burst into tears it was one of the best things I've ever done well it's very kindly to say so you know it is a very special event I've been with it since 2006 and as I was saying at the conference in 2007-20023 in Barcelona we were looking at a very different future with the WPC because it was in quite a bit of financial trouble but we but it was quite quite appropriate it was in Phoenix that we arose from these ashes and actually it was hugely successful and I've heard nothing but a very positive comments about it but thank you very much for. Can I ask you this question that we were having this discussion in 10 years time what do you think we would have learned in that 10 years? I think we would have learned in 10 years time that actually we're probably better at targeting alpha-son youth in than we were in 2026 because we've got clever ways of shuttling antibodies into the brain I think we'd have worked out that we can actually get rid of alpha-son youth in on imaging but we still haven't put people back to normal and there must be other things going on so I think we will work out how to get the alpha-son youth in antibody into the brain better I think we will have abilities to scan for it so we can see that it's gone but I imagine that we will still have found that it's not the whole story a bit like a beta and we will need to do other things to make it more effective as treatments by targeting other bits of the cascade. And generally does it worry that people don't seem to be able to sort of take the scientific method which you must be questioning you know, proposes this is the question it does it worry that people get upset by that? So I think it always worries me that people aren't prepared to debate I think part of the problem is that if I disagree with you Mark on you know some question we were debating it's a lot of people think that I'm questioning your parentage and insulting you and so it's like where it's important about I'm just debating a topic that you know it's nothing personal but a lot of people take it very personally especially if they're very going back to what Rawris said they're very passionate about something then they feel you know I've nailed my colors to the mask that's what I believe in you're saying I'm wrong so you're saying I'm stupid which is I think a misunderstanding of the debate I think it's important for us to discuss what we know and don't know I don't think we should mislead people but part of my argument was you know if I if we hadn't discussed that and we'd merely had a session on Alpha-Synuclein immune therapies for Parkinson's you know that would have been very informative but it is a biased account I mean it is based on the premise that that is the critical thing and so I think discussing these things is important and we should do it and we should do more of it. On this point in the Royal Court of Justice there is a sculpture of a judge and the thing that's feature most important features the judge has no face because they want everybody to understand is what happens in there is not personal and that's the thing is people should understand in the debate it's not personal. No and it also has to be a bit theatrical I'm sure like like cool you know I mean I'm being part of the control so was you have to play the part otherwise it is very dry scientific so the ones I went to last week it was not quite as perhaps as flame buoyant as the capacities so. My question is what have you learnt about people who have Parkinson's? So the thing I love about WP saying well I love so many things about it but I love the fact that everyone goes I'm always bumping into people and people with Parkinson's and what I love is that they're always happy to chat we're always happy to talk about things and they always tell you things that you don't necessarily know so you learn quite a lot about what the problems are I like the fact that often there are issue questions which you sort of think well that sounds like a very simple question which it is but actually the answer is incredibly complicated and I've never really thought about that before so I think it keeps you on your toes I think it's very important for the human side of this condition because I think at these meetings it can become a little bit abstract and you know this is a problem I have to solve and I don't really think of it in terms of people with this condition and what they're having to put up every day with and so I think the personal side of it and the human side of it and that's what comes across the WPC is the number of people young researchers who stand up and say you know I've never been at a meeting where I've actually met people with Parkinson's so it's hard to believe there are people working they've never met people with Parkinson's and so of course it gives them a sense of urgency which isn't there if you're just at a scientific meeting so I mean I find it very inspiring having people with Parkinson's there and they have an energy and an urgency which is very much needed and that's to me that I'm very early on I've always had it in clinic but especially with the late Thomas I mean when I first met him he was someone who very much drove that to gender and it very much ignited my already quite rampant passion for this. One more question what one thing would you like to achieve before you return? Well I wouldn't want to be prime minister I'm telling you now I'm seeing something about you. There's also also I could probably do it and still have time left to retire at the current rate of progress. with our primators. I would very much like for cell therapies to become a treatment for people with Parkinson's, so it would be in the same category as deep range stimulation. That would be one thing I would love to achieve before I retire having debated so much of my life to that, and I would very much like to have some therapy, which is modifying the disease however small before I retire, because I think once you've got that little foot in the door things will start to play from it. I haven't personally worked on that a few peripheral areas, but it's not been my main focus, so those would be my two major things I would love to see before I retire. Well, thank you Roger, most illuminating, lots of great stories, great to talk to you again. Now Movers and Shakers will be back in the pub in September for a new series, but listen out for another party profile in a couple of weeks. You've been listening to Movers and Shakers. Thanks again to Boardwave and Cure Parkinson's for their support and sponsorship. For more information about the mission to find a cure, please visit CureParkensons.org.uk. The show is produced by Nick Hilton for PODO. Our theme music is by Alex Stubbs and Cover Artwork by Tyleuket. You can find a lot more information about each episode of the podcast on our website at MoversandShakersPodcast.com.