It is a “weird”, “incredible”, but also “devastating” disease, from which patients affected “suffer terribly”. Frenchman Emmanuel Mignot, 63, has devoted his career to the study of narcolepsy, until he found the cause and thus shed some light on one of the great mysteries of biology: sleep.
His discovery has earned him the award today with a major American prize, the Breakthrough Prize, alongside the Japanese Masashi Yanagisawa, who came to similar conclusions at the same time. Thanks to this research, drugs that promise to revolutionize the treatment of narcolepsy and other sleep disorders are now being developed. 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).
30 years ago, a young graduate in medicine and science, Emmanuel Mignot decided to go to the United States during his military service, in order to study the functioning 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 “became completely fascinated”. He now teaches at Stanford University in California, where narcoleptics from around the world come to consult him.
Watson, his narcoleptic dog, helped him in his research
Stanford then has narcoleptic dogs, and he sets out to find the gene producing the disease in them. “Everyone told me I was crazy,” recalls Emmanuel Mignot, who now lives with a narcoleptic dog, Watson, whom he adopted. “I thought it was going to take a few years, and it took 10 years. Finally, in 1999, the discovery: a receptor located on 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 baptized 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 in humans. And the results are breathtaking: 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 redo it. »
A “miraculous” treatment
By giving a drug that mimics orexin in trials, the results are “truly miraculous”, says the French researcher. The patients then have “different eyes”, they are “just awake, calm”, a real “transformation. The challenge today remains to develop the formulation delivering the right dose at the right time. Applications for other diseases are also possible: for example for depressed patients having difficulty getting up, or in a coma and difficult to wake up, says the researcher.
Not all questions are answered. Emmanuel Mignot is now trying to prove that narcolepsy is triggered by the flu virus. According to him, the immune system, responsible for defending us against infections, can begin to confuse the neurons producing orexin with certain flu viruses, and end up attacking them. However, once dead, these neurons cannot be renewed, and the patients will no longer be able to produce orexin for their lifetime.