Narcolepsy: why you’ve been thinking about it all wrong

0:00This is The Guardian.

0:30Washington Wise.

0:39Narcolepsy has been used as a punchline in TV shows and Hollywood movies for decades. The joke goes, at the most inopportune time, bang, the narcoleptic falls asleep or collapses to the ground. But that isn't what narcolepsy is like in reality, and for sufferers, it's not very funny. But now, a first-of-its-kind drug has been approved in the US that targets the underlying biology. So today, why you've been thinking about narcolepsy all wrong, and how a new drug could change everything. I'm the Guardian Science Editor Ian Sample and this is Science Weekly

1:32Maddy you're going to be telling me about this new therapy but first off what is narcolepsy I mean we all have an idea of it from these sort of popular media portrayals but maybe you can set the record straight? Right. So there are actually two kinds of narcolepsy. There's type one and type two, and I'll explain the differences between them a bit later. But one thing that they both have is excessive daytime sleepiness. So this is the classic narcolepsy symptom that people will think of. It might not be falling asleep suddenly mid-sentence, but it's needing a lot more sleep during the day or feeling very, very sleepy during the day.

2:11So very often people with narcolepsy, they'll want to have naps during the day which are actually very refreshing. One of the tests for narcolepsy is putting somebody in a dark room for half an hour 40 minutes. Most of us would fall asleep but narcoleptics will fall asleep. Another symptom of narcolepsy is going into REM or dream sleep very quickly. So most of us when we fall asleep we actually go into a stage of deep sleep first but narcoleptics go almost straight into dream sleep and that means that they often suffer with things like sleep paralysis, hallucinations, very vivid dreaming, thinking that their dreams are real.

2:51But to find out more about the actual experience of what it's like to have narcolepsy, I spoke to Julie Flyger. She runs a non-profit called Project Sleep, which aims to raise awareness of sleep health and sleep issues. She also has narcolepsy. And she told me about an experience that she had before she knew that she had narcolepsy. Now, she didn't actually find out she had it until she was 24. And this experience that stuck with her, it happened just after she graduated college and she'd moved into what was her kind of first adult home. One of the first nights I lived there, I woke up in the middle of the night and I heard a burglar breaking in through the window in the living room.

3:35And then I saw my door open and a man rush at me with his arms stretch out towards my neck like he was about to attack me. But the strange thing is I just couldn't respond to him. I felt stuck. And so I just thought, oh, my God, he's about to strangle me. So I just was terrified. And then I looked up again and he wasn't there. And now I could move. So I got up and I went out and looked in the living room and there was no sign of a burglar. Then I thought, OK, I guess that's a good thing. It wasn't a burglar. Nothing happened. But I didn't know what to make of that because I'd had plenty of dreams before.

4:07But that didn't feel like a dream. It felt like it had really happened. But type one narcolepsy also has another symptom called cataplexy. And this is where when you experience a heightened emotion, say you're laughing at something that's very funny, you're surprised, you're shocked, you're angry, your muscles will suddenly weaken. You go catatonic. And it might be that your knees buckle or your head drops, or if it happens throughout your body, you might collapse to the ground. So actually, when people think of narcolepsy you know suddenly someone falling asleep it's often actually this cataplexy and people are still conscious it's just their muscles relax now when we've seen this online it's often you know narcoleptic dogs kind of randomly sort of falling down but it's kind of seen as this kind of cute or funny thing but actually Julie said the experience of it it's really unpleasant.

5:05It can be really scary when you're conscious, but you can't move. And she actually said that she wouldn't wish it on her worst enemy. There can be minor episodes that aren't, they're just kind of annoying or frustrating. Like I play a lot of tennis. And so sometimes I lose my grip on my racket as I'm about to hit a good shot. Okay. It's just sort of annoying, but the full body cataplexy where I crumble down to the ground, I'm thinking in my head, like, Julie, move your finger, move a toe. And I often want to breathe deeper because, you know, your heart and your breathing continue. Those are involuntary muscles.

5:39But I want to take a deeper breath for some reason. I feel like I might be able not to breathe, but I can't take a deeper breath. I just have to take the breath that I am having. And so and then, you know, time goes by very slowly. And then maybe after 30 seconds to a minute, it just goes away and I'm able to get up again. So it really reframes every moment that I don't feel that weakness or paralysis. I start to realize how wonderful it is not to. Wow. I mean, I can't imagine how difficult that must be. Yeah, it is really significant. You know, if you think about the excessive daytime sleepiness, it would really interrupt your life.

6:24Maybe you can only work for the first part of the day, maybe you're not able to have hobbies because you know you're so exhausted and something like cataplexy losing your muscle tone maybe dropping to the ground there are so many things where that would be really dangerous to happen in the middle of um so take something like driving where plenty of us find it difficult to stay awake sometimes we're on the on the motorway for hours at a time for an arcoleptic that's that's going to be something that's really hard something as simple as driving. And this is what Julie said about that. I think it's often so invisible how it impacts my life.

7:01It is a part of every decision I make every single day. And there's just this sense of feeling like, you know, time is very limited feeling. I feel like I have like really four to six really good hours in the morning. And I have to prioritize that really carefully to do what's most important to me. And you just feel like almost like someone's outside your house going to break in every day. You know they're coming and, you know, you're just hoping you can get one more thing done before they break in. You know, it's like that's my sleepiness. It feels like every day that I know between like 4 and 6 p.m.

7:31is coming and I'm going to have to lay down and take a nap for at least 30 minutes to an hour. And depending on the day, that can be convenient or not so convenient.

7:48so maddie are there treatments for narcolepsy already there are medicines that can help with the symptoms of narcolepsy so the excessive daytime sleepiness you might have stimulants for that try and keep you awake throughout the day for cataplexy actually there are antidepressants which help and there are different medicines as well but something that really struck me was Julie said when she was kind of figuring out her treatments she said that she kept waiting for the good option so these medicines they come along with a lot of side effects. Right so this takes us on to the new drug which treats the actual disorder rather than just the symptoms Tell me about that.

8:31Well, before I tell you about that, Ian, I'm going to tell you about how the disorder works, because I actually got a chance to speak to one of the discoverers of this, Professor Emmanuel Mignot, back in 2022 on this podcast. Now, this all happened in the 90s and he was at Stanford and he happened to have this colony of narcoleptic dogs. Now in dogs, narcolepsy is genetic. So what he did is he went into the genome and he found this one little bit of DNA and that mutation caused issues with a receptor in the brain that is activated by a molecule called orexin, also known as hypocretin. So yeah, in the dogs, this receptor wasn't working.

9:19At the same time, there was another researcher who was looking at orexin, so the brain chemical, but was interested in it because of its potential role in appetite. And so what he did is he took all the orexin out of the brains of mice, and he found that actually these mice then became narcoleptic. So it's this two bits of evidence which really showed that at the heart of type 1 narcolepsy was this chemical in the brain, orexin. What actually is orexin? I mean, what is it doing in the body? Okay, so it's a neuropeptide. It's produced by the hypothalamus. And you can kind of think of it like the master conductor of our sleep-wake cycle.

10:03So, Ian, in the morning, you wake up. And as you go about your day, you're beginning to kind of build up some sleep debt. So you'll be getting more and more tired. And as you go along, your brain, these neurons in your hypothalamus are producing orexin, and that helps you stay awake. So over the course of the day, your orexin is building up, building up, building up. You go to sleep. You go into that deep sleep. you know, the big waves going through your brain, clearing out, resting it, and your orexin drops right back down. And then you go into this REM, the dream sleep. In humans, unlike the dogs, it's not the receptor that's broken.

10:43It's the neurons. So in people with type 1 narcolepsy, it looks as if around 90 % of the neurons that would be producing orexin are damaged or broken. And what I find absolutely fascinating about this is that most researchers now believe that narcolepsy is actually an autoimmune disorder. So what they think happens is that perhaps a virus, something like that, something triggers the immune system to attack these neurons, destroy them so that you're no longer producing orexin. You can think of this like type 1 diabetes, right, where, again, it's an autoimmune condition where the immune system has attacked the cells that produce insulin.

11:28And it looks like that's similar to what's happening in narcolepsy. So presumably this new drug is mimicking orexin in the brain. Exactly that. So it's called an orexin agonist. It activates the receptors in the brain. It's as if you've got orexin again. and this has had a successful trial. It's now been approved by the FDA in the US. And what I love about this story, Ian, is that when I spoke to Professor Mignot back in 2022, he said that he thought within five years narcolepsy would become a treatable condition, that they would have a drug for narcolepsy and his prediction is pretty much bang on.

12:12Julie, who I spoke to, she actually was on the trial and she said that taking the drug she really enjoyed the wakefulness she said things just seemed sunnier she told me that people she'd spoken to had been able to take up hobbies that they hadn't before it's a pretty major step to have discovered the biology behind this condition and have a drug that treats it i even knew it was coming right like i knew within several weeks we were going to find out, right? And we were preparing as a nonprofit with, you know, beautiful graphics about all this and blog posts. Still, when I saw the news, it just like, it just means so much.

12:54And then when I posted that online and, you know, said, it's here, it's here. The comments from people around the world were so striking. Many people were saying, like, I didn't know if I would see this in my lifetime. I didn't, you know, this gives me so much hope. as a mother of a young daughter with narcolepsy in Peru. You know, I mean, from around the world, people have just known this would be the next step.

13:23Coming up, could orexin be used to treat other sleep disorders?

13:35When I was listening to you, I had a terrible feeling. I miss Thatcher. Who's really in charge? You and me, the voters? Or the bomb markets? Pretty much every centre-left politician across the West, from Andy Burnham to Zora Mamdani, has a version of this question hanging over them. How long do you think it will be before Andy Burnham is pushed aside for someone else? You know, this is the tragedy of Andy Burnham. Yanis Varoufakis was at the heart of one of the biggest financial crises of this century. It taught him some hard lessons about politics and power. There's no such thing as democracy.

14:14What there is is performance.

14:20This is Radical Thinking with me, Adit Chakraborty, a new series from The Guardian which aims to get into some of the bigger questions in politics today. Out now in your Politics Weekly feeds.

14:53Thank you.

15:02So Maddy, what happens next? So there is still a lot to learn. There were some side effects that were seen during this trial. There's lots to learn around dosage. And so around the world, there are different regulators in different countries looking at this, but there are plenty of hoops to jump through before patients are going to have access to this drug. There's also more to learn around narcolepsy. I mean, as I say, we've been talking about narcolepsy type 1. on type 2 narcolepsy. Actually, your orexin levels are totally normal and they're not sure what causes type 2 narcolepsy. So some scientists think that maybe there's other receptors involved in both types perhaps.

15:44So plenty more questions left to answer. So Maddy, it sounds like we could be hearing a lot more about orexin in the years ahead for maybe all kinds of reasons. I definitely think so. I think there's been this incredible scientific journey from I mean not even 30 years ago not knowing what caused narcolepsy to now having a first ever treatment for the condition not just treating symptoms and when it comes to sleep medicine there aren't that many if any actually medicines that treat the condition rather than the symptoms And, you know, narcolepsy, it's very rare. One in 2 ,500 people have narcolepsy.

16:29But sleep issues are big. And so I know that scientists and pharmaceutical companies will be very interested in finding out what role orexin is playing in different conditions and what these agonists could do for people. such a great story it sounds like it's just going to get better yeah i think so thanks again to maddie and to julie flyger from project sleep if you're looking for something to listen to next i'd like to recommend monday's episode of the audio long read it's looking at slime mold and the bitter debate over what constitutes intelligence

17:22and that's it for today this episode was produced by maddie it was sound designed by joel cox and the executive producer is ellie burie we'll be back on thursday see you then

17:40this is the guardian

18:09Thank you.