7 ms·

Emmanuel Mignot wins Breakthrough Prize for discovering cause of narcolepsy

191 points by crescit_eundo 4y ago

JoeAltmaier 4y ago
So, can I take an orexin pill and stay awake? The obvious question, not addressed by the article. Googling, I see only dire reviews of orexin tablets, usually due to the other ingredients. What gives? I have episodes of dire fatigue, and a way out of that mess would be very welcome.
- googlryas 4y ago
  Probably not, because you already have a functioning orexin system, and presumably whatever modulates that would just module the extra orexin as well. And anyways, who knows if consumed orexin even makes it out of your gut and past the blood-brain barrier. You could just take modafinil if you wanted to stay awake.
  - deleted 4y ago
    [deleted]
  - beaned 4y ago
    But could otexin supplements potentially help people with narcolepsy? As opposed to just keeping people who are already healthy awake longer.
- archi42 4y ago
  Judging only by that article, I'd say: Not generally. Its described as inhibiting REM sleep, not sleep or sleepiness in general. Ask a doctor to help you figure this out. Wild guess, as a random layperson on the internet with no formal qualification: Could be lack of vitamins (E, D3, B5 or B6) or a melatonin insufficiency or a irregular sleep schedule or due to psychological causes. Alcohol and other drugs have quite the impact (especially in sleep quality). Or a combination or something completely different; it's like asking "My program is slow, what can I do?" ;-)
- modeless 4y ago
  Modafinil?
- D_B_Koopa 4y ago
  No but you can trick your body into creating more Hypocretin/Orexin by taking Opiates https://www.science.org/doi/10.1126/scitranslmed.aao4953#:~:text=These%20findings%20suggest%20that%20opiate,role%20in%20maintaining%20opiate%20addiction https://www.science.org/doi/10.1126/scitranslmed.aao4953#:~:....
- devnulll 4y ago
  If I were a large military that routinely sent pilots on missions around the world, research into drugs like this would be well funded. As someone with serious sleep issues, I dream of the opposite - take a pill (or shot, or whatever) and fall into 8 hours of blissful REM sleep.
  - brippalcharrid 4y ago
    I recall that Modafinil was used in a study with US Air Force pilots and it was found that they could continue to operate for 120 hours without sleep and without significant loss of function.
  - tyre 4y ago
    the pill that solves restful sleep will be worth hundreds of billions of dollars
    - astrange 4y ago
      Trazodone works quite well for some people, is generic and isn’t particularly valuable.
      - beagle3 4y ago
        Comes with extreme dependence from what I’ve heard.
        astrange 4y ago
        Not for sleep, you take about 1/4 the dose for that. It’s generally safer than Ambien.
  - caslon 4y ago
    It's not a silver bullet, but have you tried (extremely) low-dose melatonin? Mind that most OTC melatonin capsules are at such a high dosage that they're likelier to harm your sleep than help it. https://www.gwern.net/Melatonin https://www.gwern.net/Melatonin
sorethescore 4y ago
This helps explain why Cannabidiol may help with excessive sleepiness in hypocretindeficient rats. https://pubmed.ncbi.nlm.nih.gov/31642794/ https://pubmed.ncbi.nlm.nih.gov/31642794/
modeless 4y ago
Narcolepsy is an autoimmune disease sometimes triggered by flu? Fascinating. If only we could control the immune system better, we could fix so many problems.
- godzillabrennus 4y ago
  There is so much that I hope gene hacking can do...
  - WalterSear 4y ago
    Human clinical trials of a mRNA-based vaccine for some autoimmune diseases are currently underway, fwiw.
    - mleonhard 4y ago
      Please post a link.
      - WalterSear 4y ago
        https://clinicaltrials.gov/ct2/show/NCT04916431 https://clinicaltrials.gov/ct2/show/NCT04916431 https://www.biopharma-reporter.com/Article/2021/08/02/Moderna-takes-first-autoimmune-therapeutic-candidate-into-the-clinic https://www.biopharma-reporter.com/Article/2021/08/02/Modern... https://www.clinicaltrialsarena.com/news/moderna-trial-mrna-treatment/ https://www.clinicaltrialsarena.com/news/moderna-trial-mrna-... https://www.nature.com/articles/s41467-022-31130-9 https://www.nature.com/articles/s41467-022-31130-9
  - echelon 4y ago
    Unfortunately the BCR and TCR spatial conformations that govern antigen binding affinity are a result of somatic recombination [1]. The genes edit themselves at runtime to fit their target better. It's stochastic hill climbing happening within us while we're alive. This would make it very difficult to target a specific gene to edit without having a wide blast radius. [1] https://en.wikipedia.org/wiki/V(D)J_recombination https://en.wikipedia.org/wiki/V(D)J_recombination
NaturalPhallacy 4y ago
>narcolepsy is an autoimmune disorder in which some 70,000 orexin-producing neurons in the hypothalamus are destroyed by the body’s own immune system. TIL
- sitkack 4y ago
  I wonder if Autism is also an autoimmune disorder? Or, I wonder what other diseases are autoimmune in nature? But autoimmune diseases that attack the brain or nervous system (Parkinsons?) seem like a very interesting avenue of research.
  - colechristensen 4y ago
    Autism is one of those diseases which is probably several. A cluster of symptoms which is caused by a small collection of differently or diminished functions in a set of brain systems and that altered function would be further caused by a few separate things, genetic, development environment, autoimmune, and or infection. Sort of three layers of how it presents, the brain differences that directly cause the presentation, and the underlying mechanistic causes of those differences.
  - dd36 4y ago
    Autism exploded when Back to Sleep exploded for babies. For a good chunk of babies (and their parents), forced back sleeping is hugely disruptive to sleep. So much so that the only way anyone gets rest is belly sleep on top of a parent. Sleep is important to brain development. Until proven otherwise, my hypothesis is we’re accidentally causing the spike in autism with forced back sleeping. There are studies that indirectly support this but I’m not sure of any direct studies. What got me on this path was my own son. From the time he was only a few weeks, he wouldn’t sleep for more than a few hours on his back but on his belly would sleep the whole night. The nurses in the NICU put all the babies on their tummies to get them to sleep. We threw out the doctor’s advice and tummy slept him with good air circulation and were far better off than many friends who thought their baby would die if tummy slept. Everyone before 1994 was tummy slept. What convinced me to try it was watching the nurses, reading a study on air circulation and SIDS, and that he slept great on top of me tummy down.
larsiusprime 4y ago
I have both narcolepsy and Tourette’s. There’s been some theories that Tourette’s is an autoimmune disorder too. Hopefully we’ll discover the cause of that as well one day.
- knicholes 4y ago
  I have Tourette's as well. That doesn't check out for me, because while mine continues into my late thirties, it's supposed to lessen with age.
- 77pt77 4y ago
  - whythre 4y ago
    Tourette’s tics don’t work like that. A friend of mine has it and his tics most often take the form of compulsive snorting/sneezing.
MarcoZavala 4y ago
motohagiography 4y ago
Meetings?
satisfice 4y ago
(yawn!)
- satisfice 4y ago
  Downvoted for a little self-referential humor? What is this world coming to?
bulkprotocol 4y ago
I am diagnosed with Narcolepsy, N1. It's a complete nightmare honestly. The main issue is I get TOO much REM sleep and basically almost zero NREM 3 sleep. I enter a vivid dream state within seconds of closing my eyes when sleeping. Sleep paralysis almost every day multiple times a night. Pure utter terrifying demonic nightmares and hallucinations to the point where at its worst I was too afraid to even try and sleep. I've basically been chronically sleep deprived for about the last 10 to 15 years but was only recently diagnosed a couple years ago. It's very debilitating at 33 years old and there is only one real drug that actually addresses the issue. Xyrem, really GHB, which just forces your brain to get deep sleep. It isn't a cure, but it's the closest thing we got right now. The disease has basically ruined my life but Im thankful to be where Im at. A lot of others with the disease aren't so lucky. Especially if you have no access to any real medicine. Your brain will just continue to fry itself without the needed restorative sleep.
- mongol 4y ago
  What does it mean for your life in terms of doing things that require durable concentration? For example, driving a car? Can you do that without risking falling asleep? It seems like such a cruel disease. I hope there will be better remedies ahead.
  - bulkprotocol 4y ago
    It really makes everything 100x more difficult. Especially in a cognitively intensive field. Completely killed my aspirations of being a Lawyer. I simply just could not keep up. Graduated with a terrible undergrad GPA. I was just so tired I couldn't really use my brain. Then basically limped over the finish line even though before my symptoms started I could crush reading materials. So it can definitely be a barrier for certain career choices. Luckily working in software remotely has afforded me a lot of accomodations. I truly don't know what other field I could be in that would simultaneously be flexible enough to accomodate my disability and also lucrative. Im glad I live now! I would have probably ended up Homeless if I was born 60 years ago. I'm medicated now so a lot of my symptoms are not as bad as they used to be. I am able to drive and no longer suffer from "sleep attacks" but there was a point before my diagnosis when I was so tired I could fall asleep while driving and not even notice. Very dangerous and a very scary experience. Most days I had to take naps every 90 minutes or so and self medicated with approximately 1g of caffeine a day.
mongol 4y ago
The prize money is approximately twice that of the Nobel prize. I read that it was founded by some of the richest people on the planet so perhaps not that surprising. Perhaps over time it will overtake Nobel in prestige too.
- froh 4y ago
  Alfred Nobel at his time was one of the richest people on the planet, too, so what is the point?
curiousgal 4y ago
I guess I am too cynical having read about prominent researchers faking results in similar fields.
jimnotgym 4y ago
Imagine where we could get to with medical research if we didn't waste so many super-smart people trying to target ads, harvest personal data, and high frequency trade.
- caslon 4y ago
  People who are good at programming aren't necessarily good at biology, chemistry or analysis. And, assuming that some of them did have a talent for it and computing wasn't an option, it's not likely they'd be interested in it anyway. I was pretty great at badminton yet don't play it with any frequency.
  - jimnotgym 4y ago
    You don't think there is any use for programmers on The Worlds Great Problems?
- Bakary 4y ago
  Smart people aren't a resource that can be reallocated promptly like workers in an RTS. The type of person who works at a FAANG or an investment firm isn't going to suddenly seek a career that requires more work for less money if data harvesting type jobs stop existing. They'll pivot to the next plausibly profitable gig. For structural reasons, careers that attract those types necessarily have to be in sectors of the economy are flush with cash. Governmental investment is not sufficient to create massive salaries if there isn't raw money-making capacity there to begin with. Of course, medical research has its winners but it's not nearly in the same league of certainty of opportunity than tech or finance. There should still be investment to make these jobs attractive anyway, but you are not going to have the massive shift in our common fortunes you are envisioning here. It's a bit similar to those arguments implying that without religion we'd have teleportation by now or something along those lines. It completely ignores the structural nature of the problem and how the identified 'negative' sector actually works in tandem with the rest of the society in question. It's a flawed view of how incentives really work.
  - jimnotgym 4y ago

191 points by crescit_eundo 4y ago

So, can I take an orexin pill and stay awake? The obvious question, not addressed by the article. Googling, I see only dire reviews of orexin tablets, usually due to the other ingredients. What gives? I have episodes of dire fatigue, and a way out of that mess would be very welcome.

googlryas 4y ago
Probably not, because you already have a functioning orexin system, and presumably whatever modulates that would just module the extra orexin as well. And anyways, who knows if consumed orexin even makes it out of your gut and past the blood-brain barrier. You could just take modafinil if you wanted to stay awake.
- deleted 4y ago
  [deleted]
- beaned 4y ago
  But could otexin supplements potentially help people with narcolepsy? As opposed to just keeping people who are already healthy awake longer.
archi42 4y ago
Judging only by that article, I'd say: Not generally. Its described as inhibiting REM sleep, not sleep or sleepiness in general. Ask a doctor to help you figure this out. Wild guess, as a random layperson on the internet with no formal qualification: Could be lack of vitamins (E, D3, B5 or B6) or a melatonin insufficiency or a irregular sleep schedule or due to psychological causes. Alcohol and other drugs have quite the impact (especially in sleep quality). Or a combination or something completely different; it's like asking "My program is slow, what can I do?" ;-)
modeless 4y ago
Modafinil?
D_B_Koopa 4y ago
No but you can trick your body into creating more Hypocretin/Orexin by taking Opiates https://www.science.org/doi/10.1126/scitranslmed.aao4953#:~:text=These%20findings%20suggest%20that%20opiate,role%20in%20maintaining%20opiate%20addiction https://www.science.org/doi/10.1126/scitranslmed.aao4953#:~:....
devnulll 4y ago
If I were a large military that routinely sent pilots on missions around the world, research into drugs like this would be well funded. As someone with serious sleep issues, I dream of the opposite - take a pill (or shot, or whatever) and fall into 8 hours of blissful REM sleep.
- brippalcharrid 4y ago
  I recall that Modafinil was used in a study with US Air Force pilots and it was found that they could continue to operate for 120 hours without sleep and without significant loss of function.
- tyre 4y ago
  the pill that solves restful sleep will be worth hundreds of billions of dollars
  - astrange 4y ago
    Trazodone works quite well for some people, is generic and isn’t particularly valuable.
    - beagle3 4y ago
      Comes with extreme dependence from what I’ve heard.
      - astrange 4y ago
        Not for sleep, you take about 1/4 the dose for that. It’s generally safer than Ambien.
- caslon 4y ago
  It's not a silver bullet, but have you tried (extremely) low-dose melatonin? Mind that most OTC melatonin capsules are at such a high dosage that they're likelier to harm your sleep than help it. https://www.gwern.net/Melatonin https://www.gwern.net/Melatonin

sorethescore 4y ago

This helps explain why Cannabidiol may help with excessive sleepiness in hypocretindeficient rats. https://pubmed.ncbi.nlm.nih.gov/31642794/ https://pubmed.ncbi.nlm.nih.gov/31642794/

modeless 4y ago

Narcolepsy is an autoimmune disease sometimes triggered by flu? Fascinating. If only we could control the immune system better, we could fix so many problems.

godzillabrennus 4y ago
There is so much that I hope gene hacking can do...
- WalterSear 4y ago
  Human clinical trials of a mRNA-based vaccine for some autoimmune diseases are currently underway, fwiw.
  - mleonhard 4y ago
    Please post a link.
    - WalterSear 4y ago
      https://clinicaltrials.gov/ct2/show/NCT04916431 https://clinicaltrials.gov/ct2/show/NCT04916431 https://www.biopharma-reporter.com/Article/2021/08/02/Moderna-takes-first-autoimmune-therapeutic-candidate-into-the-clinic https://www.biopharma-reporter.com/Article/2021/08/02/Modern... https://www.clinicaltrialsarena.com/news/moderna-trial-mrna-treatment/ https://www.clinicaltrialsarena.com/news/moderna-trial-mrna-... https://www.nature.com/articles/s41467-022-31130-9 https://www.nature.com/articles/s41467-022-31130-9
- echelon 4y ago
  Unfortunately the BCR and TCR spatial conformations that govern antigen binding affinity are a result of somatic recombination [1]. The genes edit themselves at runtime to fit their target better. It's stochastic hill climbing happening within us while we're alive. This would make it very difficult to target a specific gene to edit without having a wide blast radius. [1] https://en.wikipedia.org/wiki/V(D)J_recombination https://en.wikipedia.org/wiki/V(D)J_recombination

NaturalPhallacy 4y ago

>narcolepsy is an autoimmune disorder in which some 70,000 orexin-producing neurons in the hypothalamus are destroyed by the body’s own immune system. TIL

sitkack 4y ago
I wonder if Autism is also an autoimmune disorder? Or, I wonder what other diseases are autoimmune in nature? But autoimmune diseases that attack the brain or nervous system (Parkinsons?) seem like a very interesting avenue of research.
- colechristensen 4y ago
  Autism is one of those diseases which is probably several. A cluster of symptoms which is caused by a small collection of differently or diminished functions in a set of brain systems and that altered function would be further caused by a few separate things, genetic, development environment, autoimmune, and or infection. Sort of three layers of how it presents, the brain differences that directly cause the presentation, and the underlying mechanistic causes of those differences.
- dd36 4y ago
  Autism exploded when Back to Sleep exploded for babies. For a good chunk of babies (and their parents), forced back sleeping is hugely disruptive to sleep. So much so that the only way anyone gets rest is belly sleep on top of a parent. Sleep is important to brain development. Until proven otherwise, my hypothesis is we’re accidentally causing the spike in autism with forced back sleeping. There are studies that indirectly support this but I’m not sure of any direct studies. What got me on this path was my own son. From the time he was only a few weeks, he wouldn’t sleep for more than a few hours on his back but on his belly would sleep the whole night. The nurses in the NICU put all the babies on their tummies to get them to sleep. We threw out the doctor’s advice and tummy slept him with good air circulation and were far better off than many friends who thought their baby would die if tummy slept. Everyone before 1994 was tummy slept. What convinced me to try it was watching the nurses, reading a study on air circulation and SIDS, and that he slept great on top of me tummy down.

larsiusprime 4y ago

I have both narcolepsy and Tourette’s. There’s been some theories that Tourette’s is an autoimmune disorder too. Hopefully we’ll discover the cause of that as well one day.

knicholes 4y ago
I have Tourette's as well. That doesn't check out for me, because while mine continues into my late thirties, it's supposed to lessen with age.
77pt77 4y ago
- whythre 4y ago
  Tourette’s tics don’t work like that. A friend of mine has it and his tics most often take the form of compulsive snorting/sneezing.

MarcoZavala 4y ago

motohagiography 4y ago

Meetings?

satisfice 4y ago

(yawn!)

satisfice 4y ago
Downvoted for a little self-referential humor? What is this world coming to?

bulkprotocol 4y ago

I am diagnosed with Narcolepsy, N1. It's a complete nightmare honestly. The main issue is I get TOO much REM sleep and basically almost zero NREM 3 sleep. I enter a vivid dream state within seconds of closing my eyes when sleeping. Sleep paralysis almost every day multiple times a night. Pure utter terrifying demonic nightmares and hallucinations to the point where at its worst I was too afraid to even try and sleep. I've basically been chronically sleep deprived for about the last 10 to 15 years but was only recently diagnosed a couple years ago. It's very debilitating at 33 years old and there is only one real drug that actually addresses the issue. Xyrem, really GHB, which just forces your brain to get deep sleep. It isn't a cure, but it's the closest thing we got right now. The disease has basically ruined my life but Im thankful to be where Im at. A lot of others with the disease aren't so lucky. Especially if you have no access to any real medicine. Your brain will just continue to fry itself without the needed restorative sleep.

mongol 4y ago
What does it mean for your life in terms of doing things that require durable concentration? For example, driving a car? Can you do that without risking falling asleep? It seems like such a cruel disease. I hope there will be better remedies ahead.
- bulkprotocol 4y ago
  It really makes everything 100x more difficult. Especially in a cognitively intensive field. Completely killed my aspirations of being a Lawyer. I simply just could not keep up. Graduated with a terrible undergrad GPA. I was just so tired I couldn't really use my brain. Then basically limped over the finish line even though before my symptoms started I could crush reading materials. So it can definitely be a barrier for certain career choices. Luckily working in software remotely has afforded me a lot of accomodations. I truly don't know what other field I could be in that would simultaneously be flexible enough to accomodate my disability and also lucrative. Im glad I live now! I would have probably ended up Homeless if I was born 60 years ago. I'm medicated now so a lot of my symptoms are not as bad as they used to be. I am able to drive and no longer suffer from "sleep attacks" but there was a point before my diagnosis when I was so tired I could fall asleep while driving and not even notice. Very dangerous and a very scary experience. Most days I had to take naps every 90 minutes or so and self medicated with approximately 1g of caffeine a day.

mongol 4y ago

The prize money is approximately twice that of the Nobel prize. I read that it was founded by some of the richest people on the planet so perhaps not that surprising. Perhaps over time it will overtake Nobel in prestige too.

froh 4y ago
Alfred Nobel at his time was one of the richest people on the planet, too, so what is the point?

curiousgal 4y ago

I guess I am too cynical having read about prominent researchers faking results in similar fields.

jimnotgym 4y ago

Imagine where we could get to with medical research if we didn't waste so many super-smart people trying to target ads, harvest personal data, and high frequency trade.

caslon 4y ago
People who are good at programming aren't necessarily good at biology, chemistry or analysis. And, assuming that some of them did have a talent for it and computing wasn't an option, it's not likely they'd be interested in it anyway. I was pretty great at badminton yet don't play it with any frequency.
- jimnotgym 4y ago
  You don't think there is any use for programmers on The Worlds Great Problems?
Bakary 4y ago
Smart people aren't a resource that can be reallocated promptly like workers in an RTS. The type of person who works at a FAANG or an investment firm isn't going to suddenly seek a career that requires more work for less money if data harvesting type jobs stop existing. They'll pivot to the next plausibly profitable gig. For structural reasons, careers that attract those types necessarily have to be in sectors of the economy are flush with cash. Governmental investment is not sufficient to create massive salaries if there isn't raw money-making capacity there to begin with. Of course, medical research has its winners but it's not nearly in the same league of certainty of opportunity than tech or finance. There should still be investment to make these jobs attractive anyway, but you are not going to have the massive shift in our common fortunes you are envisioning here. It's a bit similar to those arguments implying that without religion we'd have teleportation by now or something along those lines. It completely ignores the structural nature of the problem and how the identified 'negative' sector actually works in tandem with the rest of the society in question. It's a flawed view of how incentives really work.
- jimnotgym 4y ago