The Frenchman awarded for a lifetime of research on narcolepsy

Emmanuel Mignot, professor of sleep medicine at Stanford University, and his narcoleptic dog, Watson.

Emmanuel Mignot is one of the world’s leading experts on narcolepsy, a sleep disorder he finds both “strange” and “fascinating”.

The Frenchman Mignot has dedicated his life to studying the causes of narcolepsy and to shed light on one of the great biological mysteries: sleep.

His discovery of the genetic and molecular causes of the disorder led to him receiving a prestigious Breakthrough award on Thursday alongside Japan’s Masashi Yanagisawa, who made related discoveries around the same time.

Because of their findings, new treatments for narcolepsy, which makes people suddenly fall asleep, and other sleep disorders are being developed.

About one in 2,000 people suffer from narcolepsy. Some may experience trance, a sudden trance state.

“I am quite proud because what I have discovered is making a huge difference to my patients,” Mignot said in a telephone interview with AFP. “It’s the best reward you can get.”

63-year-old Mignot is a sleep researcher at Stanford University in California.

Thirty years ago, when he was a medical student, Mignot met his military service requirements in France, coming to Stanford to study a French-made drug that was being used to treat narcolepsy.

At the time, he said, the disease was “virtually unknown” and no one was actively studying it.

He became “completely fascinated”.

“I told myself this is incredible, this disease, people fall asleep all the time, we have no idea why, and if we could find out the cause we could understand something new about sleep.”

Stanford was already home to a renowned sleep center, and his lab housed narcoleptic dogs, which Mignot began studying in an attempt to find a genetic cause for the disease.

Genome sequencing was very primitive at the time and “everyone told me I was crazy,” said Mignot, who currently has an adopted narcoleptic dog named Watson.

“I thought it would take a few years and in the end it took 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, similar to a lock and key.

“Remake a key”

Japanese scientist Yanagisawa, meanwhile, was studying orphan receptors, receptors of unknown function, in mice.

He found that a molecule he called orexin binds to the same receptor that Mignot detected as abnormal in dogs.

The orexin-deprived mice developed narcolepsy.

Mignot immediately began research on human subjects and found that orexin levels in the brains of narcolepsy patients were zero.

Normally the molecule is produced in large quantities during the day, especially in the evening, allowing you to fight fatigue.

“You don’t make a discovery like this twice in your life,” Mignot said. “We have found the cause of a disease.

“The advantage is that we can remake a key,” he said, referring to orexin.

For now, most patients are treated with a combination of powerful sedatives to help them sleep more soundly and amphetamines to keep them awake throughout the day.

Mignot said tests using an orexin-mimicking drug were “truly miraculous.”

Patients are fully awake and “transformed”.

The challenge is to develop the right dose to be administered at the right time.

Several companies, including Japan’s Takeda, are working on it, and drugs may be licensed in the coming years.

They could be applied to other patients – people suffering from depression, for example – who have difficulty waking up or to those in a coma.

Meanwhile, Mignot is studying whether narcolepsy could be caused by a flu virus.

The body’s immune system may confuse a flu virus with orexin-producing cells, and as a result the infection-fighting T cells attack them.

“I became interested in how the immune system works in the brain,” a field that said “is starting to explode.”

As for sleep, Mignot is fascinated by it even though he has revealed one of the great mysteries.

“What does sleep do that is so important that I have to do it every day?” she asked. “It’s true we don’t know yet.”

Scientists develop a new compound that regulates wakefulness

© 2022 AFP

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