Health: a French awarded for having found the cause of narcolepsy and its main treatment

It is a “rare”, “incredible”, but also “devastating” disease, for which affected patients “suffer terribly”. Frenchman Emmanuel Mignot, 63, has dedicated his career to the study of narcolepsyuntil we find the cause and thus shed some light on one of the great mysteries of biology: sleep.

His discovery has earned him today the award with an important American prize, revelation award, along with the Japanese Masashi Yanagisawa, who reached similar conclusions at the same time. Thanks to this research, drugs are now being developed that promise to revolutionize the treatment of narcolepsy and other sleep disorders. Narcoleptics, about one person in 2000, can’t help but suddenly fall asleep in the middle of the day. Some are also affected by sudden temporary paralysis (cataplexy).

Thirty years ago, a young medicine and science graduate, Emmanuel Mignot decided to travel to the United States during his military service, in order to study the operation of a drug then used against narcolepsy. At the time, this disease was “virtually unknown” and “no one was studying it,” he recalls. But he “was completely fascinated.” He now teaches at Stanford University in California, where narcoleptics from all over the world come to consult him.

Watson, his narcoleptic dog, helped him in his research

Stanford then has narcoleptic dogs and sets out to find the gene that causes the disease in them. “Everyone told me he was crazy,” recalls Emmanuel Mignot, who now lives with a narcoleptic dog, Watson, whom he adopted. “I thought he was going to take a few years, and it took 10 years. Finally, in 1999, the discovery: a receptor located in the brain cells of narcoleptic dogs is abnormal.

This receptor is like a lock, which only reacts in the presence of the right key: a molecule discovered at the same time by the Japanese Masashi Yanagisawa, who named it orexin (also sometimes called hypocretin). It is a neurotransmitter produced in the hypothalamus, at the base of the brain, by a very small population of neurons.

Immediately, Emmanuel Mignot carried out the first tests on humans. And the results are impressive: orexin levels in the brains of narcoleptic patients are zero. The path of action of the disease is therefore similar: in dogs, the lock is broken, but in humans, the key is missing. Which also explains why the disease can be inherited in dogs, not humans. “The advantage is that the key, we can remake it. »

A “miraculous” treatment

By administering a drug that mimics orexin in trials, the results are “truly miraculous”, says the French researcher. The patients then have “other eyes”, they are “only awake, calm”, a true “transformation”. The current challenge remains to develop the formulation that provides the right dose at the right time. Applications for other diseases are also possible: for example, for depressed patients who have difficulty getting up, or in a coma and with difficulty waking up, says the researcher.

Not all questions are answered. Emmanuel Mignot is now trying to prove that narcolepsy is caused by the flu virus. According to him, the immune system, which is responsible for defending us against infections, can begin to confuse orexin-producing neurons with certain flu viruses, and end up attacking them. However, once dead, these neurons cannot be renewed and patients will no longer be able to produce orexin throughout their lives.

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