Pod Insights Short Wave What Do Stem Cells Mean For The Future Of Parkinson's? About this episode Parkinson’s Disease affects around a million people in the United States. And that number is on the rise, in part because our population is getting older.
Dr. Claire Henchcliffe https://www.ucihealth.org/clinicians/claire-henchcliffe-1730276825, chair of neurology at the University of California, Irvine, is one of the scientists at the forefront of Parkinson’s research. She's working toward new treatment options for Parkinson’s, including recent discoveries about the potential use of stem cells.
Science correspondent Jon Hamilton https://www.npr.org/people/2100615/jon-hamilton dives into this research — and even a future where scientists can prevent the disease altogether — on the show with Henchcliffe.
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0:19 Speaker 01 You're listening to Short Wave from NPR.
0:25 Speaker 02 Hey, Short Wavers. John Hamilton here in the host chair today. In my day job as NPR's brain correspondent, I've done a lot of reporting on Parkinson's disease. It's a progressive disorder that causes difficulty with movement. It affects around a million people in the United States, and that number is on the rise, in part because our population is getting older.
0:45 Speaker 03 Parkinson's is the fastest growing out of the neurodegenerative disorders that we deal with fairly commonly as neurologists. So it's not the most common overall. That would be Alzheimer's disease. Parkinson's comes in second, but it's very concerning that it's growing so quickly.
1:02 Speaker 02 Dr. Claire Henchcliffe is the chair of neurology at the University of California, Irvine. She's one of the scientists at the forefront of Parkinson's research. She says the most visible symptoms of Parkinson's are tremors and trouble with coordination and balance.
1:17 Speaker 03 Then there's, unfortunately, the Parkinson's that you don't see. Cognition, thought processing, memory can be affected. People can have onset of depression or anxiety, whereas they've never had that before. Or there's a part of the nervous system called the autonomic nervous system that can get involved, and that affects all sorts of things. It affects how we digest our food. It can cause constipation. You can get blood pressure fluctuations. The bladder can be affected.
1:44 Speaker 02 And while people are typically diagnosed around age 50 or 60.
1:48 Speaker 03 It may start 10, 15, 20 years before we ever pick up a tremor or ever see someone slow down. Sense of smell can alter. Sleep can change. That's when the Parkinson's process in the brain has started. It's kicked off. But we don't have the wherewithal yet to be able to diagnose that process for sure.
2:14 Speaker 02 Today on the show, Parkinson's disease and new treatment options that could one day lead to a cure, or even a future where scientists can prevent the disease altogether. You're listening to Short Wave, the science podcast from NPR.
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3:56 Speaker 02 OK, Dr. Claire Henchcliffe, we're talking about Parkinson's disease. Claire, can you explain what is happening in the brain of somebody who has this disease?
4:06 Speaker 03 Sure. In Parkinson's, although there is some variability from individual to individual who suffer from Parkinson's, one of the common features is that there's a protein called alpha synuclein which is affected in the brain. It gets damaged, it gets misfolded, and it forms these alpha synuclein clumps. And these seem to be associated with damage to the nerve cells, neurons, and loss of the connections between the neurons and loss of the neurons themselves. For some reason, it seems like some parts of the brain are more vulnerable to this damage than others. And one of those parts of the brain, it's visible by eye when you look on autopsy tissue, it's called the substantia nigra, like black
4:51 Speaker 03 stuff, right, black substance. And that's where a lot of our dopamine cells sit. These cells seem to be really vulnerable to the damage. So the dopamine production decreases, and dopamine is really critical for a whole bunch of things in the brain, but one of the things that it does is it controls our coordination.
5:10 Speaker 02 When did doctors and scientists realize you could replace dopamine?
5:14 Speaker 03 The gold standard medication that we have right now, it's called carbidoproliverdopa. The leverdopa gets up into the brain, replaces your dopamine. This has been around since the 50s and 60s. But the idea about replacing dopamine was known from way before then.
5:36 Speaker 02 Presumably, treatment has evolved over time. Can you talk a little bit about what's happened since those first treatments?
5:43 Speaker 03 Yeah. Over time, it was realized there are complications that arise with long-term use of leverdopa. So we've seen a lot of new drugs coming up. The mainstay for oral drugs is still looking at dopamine. So we've never really gotten away from that. Now, aside from that, deep brain stimulation has been approved for use in Parkinson's for decades now. Just this year, we had approval of a new way of dealing with deep brain stimulation.
6:19 Speaker 03 And you can actually, as well as delivering the current, deep down in the brain that helps the symptoms of Parkinson's, you can actually record from it as well. And it works on a on a feedback loop, so it can self-adjust the amount of stimulation that it's giving.
6:35 Speaker 02 Wow.
6:35 Speaker 03 Wow, indeed.
6:36 Speaker 02 We had a listener to the podcast write in, talking about all of the sort of non-medically sanctioned treatments that are offered. And the internet is full of things that claim to help people with Parkinson's. Do any of those things work? Any non-medical treatments?
6:54 Speaker 03 Unfortunately, as many of these supplements have come into clinical trials, we've been burned over and over again as investigators. And what looked really promising, even through a phase one or a phase two clinical trial, when you get it into that pivotal phase three, it it just seems to crash and burn. I suspect that the variability that I mentioned in Parkinson's also plays a part in this, and we're not sufficiently managing to individualize, get the right treatment to the right patient. And outside of the oral supplements, some of the devices that are being offered, it's really hard to know. We don't have publications that have been peer reviewed. So I think I like to keep
7:39 Speaker 03 an open mind, but I also like to keep a healthy dose of skepticism when I'm trying to assess these.
7:45 Speaker 02 What about various forms of exercise? I've read things about dance and boxing. What is the story behind all that?
7:53 Speaker 03 I'm a huge fan. And there is a rich, rich literature in looking at exercise and its effects in Parkinson's, as well as healthy people, as we're all getting older. I've worked myself with dance, like Dance for Parkinson's Disease, and we actually published a small paper, and we could see some benefits in a in a short, small, short-term trial. I'll just say, in terms of having large clinical trials, the sort that we would demand from drugs, we don't have that sort of clinical trial with the exercise. But I do think, given all the evidence that's out there, exercise is a it's a short bet.
8:38 Speaker 02 Claire, you're involved in one area of Parkinson's research that seems really promising: stem cells. Tell me a little bit about how they work.
8:46 Speaker 03 Absolutely. So
8:49 Speaker 03 There are different types of these called, they're called pluripotent stem cells. They can make all different things. They can make heart muscle. They can make nerve cells. They can make skin cells, all sorts. We knew about that type of cell um since the nineteen nineties. And then there's a major breakthrough in the two thousands where it was discovered that as opposed to having to go back to an embryo, you could actually take adult cells either from the skin or from the blood and program them or deprogram them, I guess, in the lab to become stem cells. Then they've got the possibility to become anything. And these are called IPS induced pluripotent cells.
9:32 Speaker 03 And to all intents and purposes, they they look and act like the human embryonic stem cells. So we've got these different potential sources now.
9:41 Speaker 02 Walk me through a stem cell transplant for Parkinson's. If some, if a patient has this and they they qualify, where do the stem cells come from? Where do they get put in? How does the whole thing work?
9:52 Speaker 03 Yeah, okay, so um this is all experimental. This is all clinical trials. We're not asking people to pay. We're not pretending that this does something that we don't know that it does. So when the person comes to me, the first bit is brutally honest conversation. And I also need to figure out with them, are they someone where the risk benefit ratio is going to be acceptable? And then from the other side, while I'm doing that, my colleagues on the um science um and uh cell production side will have already dealt with the cell production, the quality testing, the cryopreservation. So we've got banks of cells that we can dip into as needed.
10:37 Speaker 03 And then the cells are brought out of there, they're they're thawed as they come into the um operating room. It takes a long time. The patients are under general anesthesia. And then we um had countered on and we almost always achieved um an overnight stay to get people back up on their feet, checked out by physical therapy, and then they're out until they start coming back for the evaluations. And at that point, um it it's really watching like a hawk for any expected and unexpected side effects.
11:11 Speaker 02 So give me a sense of how many people have had these stem cell transplants and and does it work?
11:17 Speaker 03 Yeah. So very few right now have had the cell transplants. And I should clarify, these are, these are dopamine producing cells that have been kind of coaxed in the lab to develop from stem cells. So when these dopamine producing cells go in, we've now had 12 people from our clinical trial that was funded by Blue Rock. There have been seven people with Parkinson's who've been, their cases have been published and they underwent surgery using the IPS cells that were developed in Japan to produce dopamine cells.
11:57 Speaker 03 And we know, although not quite yet published, but we know that there are at least two other groups who have a small number of people who have also received cells.
12:09 Speaker 02 And so the, the two groups you mentioned that had published, you're one of them. The, it was pretty, the, the symptoms got better, right?
12:19 Speaker 03 We have to be cautious about how we interpret this. So I think the way, the, the progression of clinical trials is to start by looking at safety and tolerability in a small number of patients. And that's what our primary aim was. Of course, we wanted to learn about what the effects of the cells might be expected and unexpected. And what we'd expected was, we thought that the amount of time that people would spend in the day, whether medicines are not controlling their symptoms, we thought that would reduce. We thought they would have more, what we call on time, where their Parkinson's symptoms are nicely controlled.
13:00 Speaker 03 We thought that if the medicines were not working, the symptoms, that, that the amount of time would not only reduce for that off time, where the medicine's not working, but also the off period would not be as severe. So people would not feel that downtime so much. I'm happy to say that for some of the participants, that actually seems to have been the case.
13:26 Speaker 03 Um. Now, could it be placebo? And we can't rule out a placebo effect. We didn't have a placebo group in there. Some of the effects have been sustained for a long time. Right now, that would argue against placebo. But we do know that when you you provide something that is very interventional, the placebo effect can kind of go on. So I'm really excited and at the same time cautious.
13:51 Speaker 02 And so getting back to to where we started is, is this the path you see to having something that could prevent the disease from developing? Obviously, if you got replace the cells before the symptoms showed up? Or if symptoms showed up, replace the cells and get rid of the symptoms?
14:08 Speaker 03 So I think to begin with, it's going to be, well, the symptoms have shown up. We can replace the cells and get rid of those symptoms. Um, just want to speak to a limitation of the current approach, which is focused on all those dopamine symptoms, right? So we believe that this approach should be able to help with the slowing, the incoordination, um, the, um, uh, some of these these symptoms that people get when they're off, the stiffness, the cramps. Um, we don't have reason to think that it's going to help with cognition, for example. It's a different part of the brain. Unless there's some unanticipated indirect effect, then this is not going to be a magic bullet for all of the effects of Parkinson's disease
14:53 Speaker 03 and the more widespread pathology that comes with Parkinson's. And people are already using gene therapy to deliver what may be protective factors, like, um, there's a protein called GDNF, um, into the brain. So could we meld these two approaches, if you like? And if we could do that and prevent the spread of pathology and keep the cells healthy, well, that would be a precursor to being able to go back, find people who are at high risk of getting Parkinson's, either because of genetics or because of something else we know about them, and then introduce, um, a, um, an intervention like that. In all the years that I've worked in Parkinson's,
15:37 Speaker 03 I'll just say I have never seen such a rich pipeline and I've never seen such rapid advances. So I think we have to, we have to think big.
15:47 Speaker 02 It sounds like you are. Claire, thank you so much for talking. You, you tell a wonderful story.
15:53 Speaker 03 Thank you for having me. And what a privilege it's been to be able to work with the people with Parkinson's, because without them, we're not doing any of this.
16:07 Speaker 02 This episode was produced by Rachel Carlson and edited by Amina Khan. Tyler Jones checked the facts. Jimmy Keely was the audio engineer. Beth Donovan is our senior director and Colin Campbell is the senior vice president of podcasting strategy. I'm Jon Hamilton. Thanks for listening to Short Wave, the science podcast from NPR.
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