When you think of narcolepsy, you probably think of people falling asleep at seemingly
random times, but it’s actually much more than that.
It causes hallucinations, insomnia and sleep paralysis and can be triggered by moments
of joy.
Oh, and the key to understanding it came from studying man’s best friend.
Narcolepsy is a neurological disorder where your brain loses its ability to control its
sleep-wake cycle.
This includes symptoms like cataplexy, a condition that causes uncontrollable muscle weakness
or paralysis which is often triggered by excitement or laughter, and hypnagogic hallucinations,
which is basically when you start to dream before you fall asleep.
That's great.
It would be white wine.
Hello my name is Emmanuel Mignot, I'm a professor at Stanford.
I'm a medical doctor and a researcher and I've been working for 30 years on a sleep
disorder called narcolepsy.
Narcolepsy is a very strange disorder...
So initially people thought it was even a type of seizure.
But then when people looked they said no, it’s not seizures, they are more sleeping.
But narcolepsy isn’t really about falling asleep, it’s about not being able to stay
awake - and the role of a specific neuropeptide made in a very small region of the brain.
The region that’s called hypothalamus which is just above the optic nerve.
So very important, very primitive part of the brain that regulates sleep, appetite,
very basic physiology.
And these cells that produce hypocretin are all there.
Hypocretin, also known as orexin, is a neuropeptide that is responsible for keeping you awake.
Once released, hypocretin travels throughout the brain activating other cells, like those
responsible for creating things like dopamine, histamine, serotonin and norepinephrine.
These brain cells then start to fire more, releasing their respective chemicals which,
in turn, further stimulate your brain.
And the other thing it does is and that's a little bit less understood but it can also
control your dreaming.
So is that when this chemical is absent, dreams come too strongly and too fast.
And that's why you have all these weird symptoms of dreaming too much and the dreams are almost
real and sometimes you are paralyzed at the wrong time because you are paralyzed during
dreaming.
So the two main function of this chemical is: one is to stay awake voluntarily and the
second one is to control your dreams so that your dreams don't come too fast into wakefulness.
And this chemical is very important...and when it's not there you have narcolepsy.
It took me 10 years to figure out the cause of narcolepsy in terms of losing the hypocretin
cells.
Then it took me 15 years to figure out why the cells were missing.
This is the Pandemic H1N1/09 virus, but you may know it as the swine flu.
Dr Mignot and team noticed that during the 2009 swine flu pandemic, there was a significant
uptick in narcolepsy cases.
And that I have to say we discovered by chance that it seems to be the flu that triggers
this abnormal reaction…
In fact we discovered that there is a piece of this 2009 swine flu that looks very much
like hypocretin.
And then instead of attacking just the flu the cells start to attack hypocretin and then
it kills the cells that produce it.
And then once the process is started then it starts to be more and more inflamed and
then it kills the hypocretin cell thinking is the flu infected cells and then you don't
have anymore hypocretin cells and then you have narcolepsy for the rest of your life.
The immune system attacking hypocretin producing cells is why many people categorize narcolepsy
as an autoimmune disease.
But this response doesn’t happen to everyone who gets the flu virus.
In fact, I like to say that to develop narcolepsy, you have to have a series of bad luck.
You know because really your immune system has to be primed a certain way and you have
to get the flu at a certain time together with a certain immune background to genetic
background to really develop narcolepsy.
So it’s like a perfect storm to develop narcolepsy.
But humans aren’t the only ones to develop narcolepsy.
It can affect dogs and as well as horses and bulls.
In fact, by studying narcolepsy in dogs, Dr Mignot and others were able to initially make
the connection between hypocretin and staying awake.
And at the end you know one breakthrough was actually which found a family of dachshund
with narcolepsy.
I still remember the dog.
It was Fritz.
Narcolepsy in dogs is a genetic disease, so researchers were able to map the mutation
that caused narcolepsy in dog families, notably in Fritz, and found a very important mutation.
And then finally we discovered that this gene was a mutation in a receptor for a chemical
called orexin, or hypocretin.
From there Dr Mignot and his team were able to focus their study of narcolepsy in humans
and eventually come to their breakthrough connecting it to the hypothalamus and the
swine flu.
Fritz was really key.
Thanks Fritz...good dog.