It is a “strange”, “unbelievable”, but also “devastating” disease, from which affected patients “suffer terribly”. Frenchman Emmanuel Mignot (63) dedicated his career to study narcolepsyuntil the cause is found and thereby sheds some light on one of the great mysteries of biology: sleep.
Today, his discovery earned him a top American award, breakthrough prize alongside 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 fall asleep suddenly in the middle of the day. Some also suffer from sudden temporary paralysis (cataplexy).
30 years ago, a young medical and science graduate, Emmanuel Mignot, decided to go to the United States during his military service to study the workings of a drug then used against narcolepsy. At the time, the disease was “virtually unknown” and “no one was studying it,” he recalls. But he was “absolutely fascinated”. He now teaches at Stanford University in California, where narcoleptics from all over the world go to consult him.
His narcoleptic dog Watson 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 I was crazy,” recalls Emmanuel Mignot, who now lives with Watson, a narcoleptic dog he adopted. “I thought it would take a few years and it took 10 years. Finally, in 1999, a discovery: a receptor located on the brain cells of narcoleptic dogs is abnormal.
This receptor is like a lock that only works in the presence of the right key: a molecule discovered at the same time by the Japanese Masashi Yanagisawa and named orexin (sometimes also called hypocretin). It is a neurotransmitter produced in the hypothalamus, at the base of the brain, by a very small population of neurons.
Emmanuel Mignot immediately performed the first tests on humans. And the results are breathtaking: orexin levels in the brains of narcoleptic patients are zero. The path 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. »
By administering a drug that mimics orexin in trials, the results are “truly miraculous,” says a French researcher. Patients then have “different eyes”, they are “simply awake, calm”, a real “transformation”. The challenge today remains to develop a formulation that delivers 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 who are in a coma and have difficulty waking up, the researcher says.
Not all questions are answered. Emmanuel Mignot is now trying to prove that narcolepsy is triggered by the flu virus. The immune system, responsible for our defense against infections, he says, can start mistaking orexin-producing neurons for some flu viruses and end up attacking them. However, once these neurons die, they cannot be regenerated and patients will no longer be able to produce orexin for life.