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Washington (AFP) – Emmanuel Mignot is one of the world’s leading experts on narcolepsy, a sleep disorder he finds both “strange” and “fascinating”.
Born in France, Mignot has devoted his life to researching the causes of narcolepsy and unraveling one of the great biological mysteries – sleep.
His discovery of the genetic and molecular causes of the disease led to him receiving a prestigious Breakthrough Prize on Thursday, along with Masashi Yanagisawa of Japan, who made similar discoveries around the same time.
Their discoveries are leading to the development of new treatments for narcolepsy — which causes people to fall asleep suddenly — and other sleep disorders.
About one in 2,000 people suffer from narcolepsy. Some may experience catalepsy – a sudden trance-like state.
“I’m quite proud because what I’ve discovered is making a tremendous difference to my patients,” Mignot said in a phone interview with AFP. “It’s the best reward you can get.”
Mignot, 63, is a sleep researcher at Stanford University in California.
Thirty years ago, while a medical student, Mignot fulfilled his military service in France by coming to Stanford to study a French-made drug used to treat narcolepsy.
At the time, he said, the disease was “virtually unknown” and nobody was actively studying it.
He was “completely fascinated”.
“I said to myself it’s incredible, this disease, people fall asleep all the time, we have no idea why, and if we could find out the cause, maybe we would understand something new about sleep.”
Stanford was already home to a renowned sleep center, and its lab housed narcoleptic dogs, which Mignot began studying to find a genetic cause of the disease.
Genome sequencing was very primitive back then and “everyone told me I was crazy,” said Mignot, who currently has an adopted narcoleptic dog named Watson.
“I thought it was going to take a couple of years, and it ended up taking 10.”
In 1999, Mignot found a mutation in the genome of narcoleptic dogs. It was located on membrane receptors in the brain that respond to molecules outside the cell, much like a lock and key.
‘Remake a Key’
Meanwhile, the Japanese scientist Yanagisawa studied orphan receptors – receptors of unknown function – in mice.
He discovered that a molecule he named orexin binds to the same receptor that Mignot had identified as abnormal in dogs.
Mice deprived of orexin developed narcolepsy.
Mignot immediately began research on humans and found that the levels of orexin in the brains of narcolepsy patients were zero.
Normally, the molecule is produced in large amounts during the day, especially in the evening, to fight fatigue.
“You don’t make a discovery like this twice in your life,” said Mignot. “We have found the cause of a disease.
“The advantage is that we can recreate a key,” he said, referring to orexin.
Right now, most patients are treated with a combination of powerful sedatives to help them sleep better and amphetamines to keep them awake during the day.
Mignot said tests of a drug that mimics orexin have been “really wonderful”.
Patients are fully awake and ‘transformed’.
The challenge is to develop the right dose at the right time.
Several companies, including Japan’s Takeda, are working on it, and drugs could be approved in the next few years.
They could also be used in other patients who, for example, are depressed and have trouble waking up, or in patients who are in a coma.
Meanwhile, Mignot investigates whether narcolepsy might be caused by a flu virus.
The body’s immune system can mistake a flu virus for the cells that produce orexin, and T cells that fight infection attack them as a result.
“I’m interested in how the immune system works in the brain,” a field he said is “starting to explode.”
As for sleep, Mignot remains fascinated by it even though he has uncovered one of the great mysteries.
“What makes sleep so important that we have to do it every day?” he asked. “It is true that we still do not know.”
© 2022 AFP
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