Briefing Chat: New narcolepsy drug could unlock host of novel brain therapies

**Nick Petrichow** (0:05)
Hello and welcome to the Briefing Chat Podcast, the Friday show where we talk about a couple of stories that have been highlighted in the Nature Briefing, Nature's daily roundup of the latest science news. And here with me to talk all things science this week is Maren Hunsberger. Maren, hi, how's it going?

**Maren Hunsberger** (0:21)
Hi, good, happy to be here as always.

**Nick Petrichow** (0:23)
Well, thank you for joining me. And I'm very curious what you've brought to the Briefing Chat Podcast this time.

**Maren Hunsberger** (0:28)
I'm really excited about this one. I mean, I'm excited every week because I think they're all really cool, but this one was a really interesting one. I'm assuming you've heard of narcolepsy.

**Nick Petrichow** (0:38)
That's where you like randomly fall asleep. Maybe not so random, but you fall asleep when you don't want to, I think.

**Maren Hunsberger** (0:43)
No, yes, that's basically it. It's a little more complex than that. There's basically two types of narcolepsy. There's type one and type two. And that's actually relevant. It's going to come into play later. But essentially it's characterized by excessive daytime sleepiness. You have a lot of trouble staying awake during the day. You may fall asleep unexpectedly and without any preamble into a deep sleep for small chunks of time. You may not be able to sleep at night. You may have night terrors or sleep paralysis. Some people have some hallucinations. And in type one narcolepsy, you also experience something called cataplexy, which is really interesting. It's where you lose muscle tone, so the ability to have your muscles maintain their stiffness. When you're experiencing an extreme emotion, like laughter.

**Nick Petrichow** (1:30)
Oh, so this is when you're awake, you could just not have control of your muscles.

**Maren Hunsberger** (1:34)
That's correct. And that's called cataplexy. And so people have been looking into this for a really long time, right? Narcolepsy is very disruptive to your life, as you might imagine. I actually, exactly. I have a friend who has it, actually, and she described, you know, one of the reasons that she ended up getting diagnosed was because she found herself falling asleep at traffic lights for tiny little increments of time, which is, of course, like, yeah, very unsafe and very disruptive.
So people have been looking into this for a long time to try and figure out what the issue is. And our treatments for narcolepsy up until now have primarily been treating the symptoms. So people get prescribed stimulants to help them stay awake during the day. People get prescribed sleep aids to help them fall asleep and stay asleep at night. But that's not really been looking at what the root cause of this might be. Now there's a new drug that has been FDA approved is the first of its kind that is designed to treat the root cause of narcolepsy.

**Nick Petrichow** (2:27)
Oh, okay. So this is something that could potentially be used in people in the US. It's got that approval straight away and could actually treat root cause. But what is the root cause, I suppose?

**Maren Hunsberger** (2:38)
It's a great question. And it's different between type one and type two, which is why I made that distinction early on. In type one, many scientists believe that the root cause of narcolepsy is because of a lack of a peptide called orexin, which is produced in your brain. That's supposed to help with your sleep-wake cycle. It basically regulates when we fall asleep and stay asleep and when we wake up.
But in type one narcoleptics, their brains are missing this orexin. So this drug is essentially acting, some people are comparing it to the GLP-1 drugs that are on the market, because GLP-1 drugs are technically, as you and I know Nick, GLP-1 agonists. So essentially they mimic the function of the GLP-1 hormone in your gut to sort of regulate satiety and how full you feel and how quickly your food is digested. With this drug, it's an orexin agonist. So it mimics the function of orexin in your brain, which is missing from people with type 1 narcolepsy.

**Nick Petrichow** (3:34)
Okay, okay. So it's just trying to replace that thing that is missing, I guess.

**Maren Hunsberger** (3:38)
Exactly. And what's interesting is that many scientists are saying, you know, type 2 has a different mechanism probably. There's all kinds of other neurons and a couple of different other pathways that scientists are still looking at as potentially being involved in narcolepsy, especially type 2 So it's not that this is the one singular root cause, but it's definitely involved. And in these clinical trials that people, you know, tested this drug in, it has been, you know, very effective. Some of the folks who were interviewed for a piece in Nature about it said that it's completely changed their lives. Some of the scientists involved say that essentially, when taking this drug, narcolepsy patients become more or less indistinguishable from quote unquote normal folks in their sleep cycle, which is absolutely huge for the quality of life of these folks who struggle with this disorder. And that is, you know, in the millions of people worldwide.