Researchers who uncovered cause of narcolepsy honored
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Two researchers who did groundbreaking work on narcolepsy, the neurological disorder that triggers sudden sleep attacks, won a prestigious science award Wednesday.
An Albert Lasker Prize—often described as a possible hint at a Nobel—went to Emmanuel Mignot of France and Japan's Masashi Yanagisawa for their work in the 1990s.
Working with very different approaches, they reached the same conclusion as to the cause of narcolepsy: In people, it is a missing brain chemical.
Their studies opened the way for treatment of the condition and revolutionized the still-nascent field of sleep science.
Mignot remembers considering the disorder, characterized by sleep attacks and sudden loss of muscle tone in both animals and humans, as "really weird" and set out to find what causes it.
"Everyone told me it was crazy," the Stanford University School of Medicine professor told AFP. "But I really believed in it."
He spent a decade studying the genome of dogs, in which narcolepsy can be hereditary, in hopes of finding the culprit gene. A popular video in France these days shows a dog running playfully in a yard, then abruptly collapsing in sleep.
This needle-in-a-haystack challenge finally paid off for Mignot in 1999.
Around the same time, Yanagisawa identified the neurotransmitter orexin, also called hypocretin, which at first he thought was involved in the feeling of hunger. But it turns out the absence of this substance caused narcolepsy in mice.
"That was a very dramatic and beautiful convergence of science," Yanagisawa, a doctor and biologist affiliated with Tsukuba University in Japan, told AFP.
Missing key
The two men's complementary work zeroed in on the underlying mechanism behind narcolepsy.
They found that in people and mice with narcolepsy, orexin, which is normally produced by the hypothalamus at the base of the brain, is absent.
In dogs, orexin is present, but in cases involving the disorder, this molecule, which acts as a sort of key, cannot open the lock that corresponds to it because the lock is jammed with a genetic mutation.
This finding—that narcolepsy is genetic in nature—shook the medical world.
"Before then, sleep had never been a field for genetics and molecular biology," Yanagisawa said.
Until then, researchers had simply made lesions in the brain to see what effect this had on sleep, he said.
So the discovery of a genetic root for narcolepsy opened up new ways of studying and treating sleep problems.
After decades of work, a drug targeting orexin deficiency in people with what is known as type 1 narcolepsy was approved this year in the United States, China and Japan.
"This was a game changer," Mignot said, adding that his patients improved dramatically. Many of them had lives so disrupted by the disorder that they could not, for example, enjoy hobbies.
"Suddenly they are back to normal. I have some who started playing hockey or dancing. It gave them back their freedom," Mignot said.
A real mystery
Other treatments that block the effects of orexin—it has a stimulating effect that maintains wakefulness—have also emerged to help people suffering from insomnia, Yanagisawa said.
More progress might come as researchers learn more about sleep, he said.
Indeed, more than 30 years after doing their work—which was also honored with a so-called Breakthrough Prize in 2023, known as the Oscars of science—many questions about sleep remain.
The mechanisms of shifting from sleep to being awake are now well understood, but what actually triggers this shift is not, Yanagisawa said.
"It is a real mystery," he said.
Unknowns also remain in the study of narcolepsy, such as why people who suffer from it lack orexin.
Mignot thinks this is caused by an attack from the body's immune system, and these days he is trying to prove this assault is linked to the flu virus.
Then there is the question of what causes people with narcolepsy to suffer sudden onsets of sleep—episodes often associated with feeling strong emotions like surprise, laughter or anger.
"Normally, when people find something funny," Mignot said, "they get ready to respond with a joke."
"We don't really understand why they fall asleep."
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