A new treatment for narcolepsy
When the inability to resist sleep becomes a nightmare! This is the daily reality for almost 20,000 people in France suffering from narcolepsy. To better treat this disease, sleep neurologist Yves Dauvilliers and his team at Montpellier University Hospital have just developed an innovative treatment.
The most severe form of somnolence in men, narcolepsy generally occurs in people aged between 15 and 20. Although difficulty staying awake is the main symptom of this neurological condition, it is not the only one. Sleepiness can sometimes be accompanied by weight gain, hallucinations, sleep paralysis and frequently cataplexy, in other words "loss of muscle strength linked to favorable emotions such as laughter", explains Yves Dauvilliers of the Neuropsychiatry: Epidemiological and Clinical Research Laboratory, and coordinator of the four narcolepsy reference centers recognized by the French Ministry of Health, of which the Montpellier University Hospital is the leader.
80,000 neurons destroyed
An autoimmune disease of genetic and environmental origin, narcolepsy and its mechanisms have only been well known to researchers for some twenty years. The human brain contains over 100 billion neurons," explains Yves Dauvilliers, "and narcolepsy destroys 80,000 of them by targeting hypocretin neurons exclusively.
Hypocretin is a neurotransmitter whose main role is to stimulate wakefulness. "It's because hypocretin neurons are activated that you can have wakeful behaviors, in other words eating, chatting, walking," stresses the researcher. Fortunately for narcoleptics, hypocretin isn't the only neuron that plays this role, otherwise they'd be asleep 24/7."
In fact, other neurotransmitters such as dopamine, noradrenaline, histamine and acetylcholine can partially take over when the hypocretin neurons disappear. The aim of narcolepsy treatments is therefore to increase the presence of these molecules in the synaptic gap linking two neurons, in order to stimulate the wakefulness message. Neurons release their neurotransmitters in the pre-synaptic button, but then recapture some of them to prevent new protein synthesis," explains Yves Dauvilliers. Medication will prevent the reuptake of these neurotransmitters, thereby increasing their number and promoting wakefulness.
Avoiding the risk of side effects
Amphetamines, which inhibit the reuptake of dopamine, were used as the first treatment for narcolepsy. Causing significant side effects, they were gradually replaced by Ritalin, also prescribed for hyperactivity, and today by Modiodal or Wakix, which increase histamine levels.
While the latter treatments are effective, their effects are not always sufficient or long-lasting. "Sometimes there's a kind of escape," describes the researcher, " over time, people become a little drowsy again. Unfortunately, if you increase doses too much, you risk side effects such as headaches, irritability, high blood pressure...". Hence the need for a new treatment.
It's now a done deal. After 4 years of work and testing at the Montpellier reference center, the new drug, developed in collaboration with JAZZ Pharmaceuticals, was granted marketing authorization in the USA last March, and should be approved in Europe by the end of the year. This innovative treatment no longer acts simply on dopamine reuptake, but also on noradrenaline, and has therefore proved to be "highly effective, well tolerated and without escape over time, at least over the one-year evaluation period", enthuses Yves Dauvilliers.
Double the sleep resistance
For three months, the 250 patients making up the cohort were able toself-assess using the Epworth scale. This questionnaire covered eight everyday situations in which patients were likely to fall asleep: reading, watching TV, driving, etc. Their resistance to sleep was also tested in the laboratory. Their resistance to sleep was also tested in the laboratory. Sitting in a room, without any stimulation and bathed in subdued light, the goal was for them to go 40 minutes without falling asleep. This operation was repeated four times, each two hours apart. "In such conditions, narcoleptics generally fall asleep after 10 or 12 minutes. Previous treatments increased their resistance by 3 or 4 minutes, with this one it's doubled", reports Yves Dauvilliers. All the more reason for Montpellier to earn its nickname of "the city where the sun never sets", including for narcoleptics.
A difficult diagnosis
At the forefront of research, the Montpellier Narcolepsy Reference Center is also working to improve diagnosis of the disease. "Only a third of narcoleptics are treated. The delay in diagnosis is 8 to 10 years," says Yves Dauvilliers, a sleep specialist at the CHU. "People think that sleep deprivation is the only factor that causes drowsiness, but at 15 or 20 it's not normal to be drowsy in class if you've had enough sleep at night". Hence the importance, at an age when one's professional future is often at stake, of ensuring that this sleepiness does not conceal an underlying illness.