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Hey, Shortwavers.
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.
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 But it's very concerning that it's growing so quickly.
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.
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.
And while people are typically diagnosed around age 50 or 60, 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.
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 Shortwave, the science podcast from NPR.
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Okay, 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?
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 is visible by eye.
When you look on autopsy tissue, it's called the substantia nigra, like black stuff, right?
Black substance tissue.
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.
When did doctors and scientists realize you could replace dopamine?
The gold standard medication that we have right now is called carbidopa levodopa.
The levodopa 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.
Presumably, treatment has evolved over time.
Can you talk a little bit about what's happened since those first treatments?
Yeah.
Over time, it was realized there are complications that arise with long-term use of levodopa.
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.
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 feedback loop so it can self-adjust the amount of stimulation that it's giving.
Wow.
Wow, indeed.
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?
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 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 an open mind, but I also like to keep a healthy dose of skepticism when I'm trying to assess these.
What about various forms of exercise?
I've read things about dance and boxing.
What is the story behind all that?
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 is.
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 short bet.
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.
Absolutely.
So there are different types of these.
They're called pluripotent stem cells.
They can make all different things.
They can make heart muscle.
They can make no cells.
They can make skin cells, all sorts.
We knew about that type of cell since the 1990s, and then there's a major breakthrough in the 2000s 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.
And to all intents and purposes, they look and act like the human embryonic stem cells.
So we've got these different potential sources now.
Walk me through a stem cell transplant for Parkinson's.
If a patient has this and they qualify, where do the stem cells come from?
Where do they get put in?
How does the whole thing work?
Yeah.
Okay.
So 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 science and cell production side will have already dealt with the cell production issue, the quality testing, the cryopreservation.
So we've got banks of cells that we can dip into as needed.
And then the cells are brought out of there.
They're thawed as they come into the operating room.
It takes a long time.
The patients are under general anesthesia.
And then we had counted on and we almost always achieved 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, it's really... watching like a hawk for any expected and unexpected side effects.
So give me a sense of how many people have had these stem cell transplants and does it work?
Yeah.
So very few right now have had the cell transplants.
And I should clarify 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 whose cases have been published, and they underwent surgery using the iPS cells that were developed in Japan to produce dopamine cells.
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.
And so the two groups you mentioned that had published you're one of them the symptoms got better right.
We have to be cautious about how we interpret this.
So I think 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.
We thought that if the medicines were not working, the symptoms, 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.
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 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.
And so getting back 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 replaced the cells before the symptoms showed up or if symptoms showed up, replace the cells and get rid of the symptoms.
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.
I 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.
Some of these symptoms that people get when they're off, the stiffness, the cramps.
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 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 a protein called GDNF, 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 an intervention like that.
In all the years that I've worked in Parkinson's, 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 think big.
It sounds like you are.
Claire, thank you so much for talking.
You tell a wonderful story.
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.
This episode was produced by Rachel Carlson and edited by Amina Khan.
Tyler Jones checked the facts.
Jimmy Keeley was the audio engineer.
Beth Donovan is our senior director.
And Colin Campbell is the senior vice president of podcasting strategy.
I'm John Hamilton.
Thanks for listening to Shortwave, the science podcast from NPR.
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I'm the host of Wildcard from NPR.
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But these days, I love it.
Gosh.
Give me a minute.
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