A major breakthrough in the treatment of narcolepsy
While difficulty staying awake may seem trivial, it is actually the primary symptom of one of the most severe sleep disorders: narcolepsy. In Montpellier, the Reference Center for Narcolepsy and Rare Hypersomnias (Inserm/University/Montpellier University Hospital), led by Yves Dauvilliers, is conducting cutting-edge research on this condition. The neurologist and his colleagues, in partnership with Takeda Laboratories have just conducted a groundbreaking study on a promising treatment. The findings were published in the New England Journal of Medicine on July 27, 2023.
Nearly 20,000 people in France have narcolepsy, a condition that typically develops between the ages of 15 and 20. While difficulty staying awake is the main symptom of this neurological disorder, it is not the only one. Sleepiness can sometimes be accompanied by weight gain, hallucinations, sleep paralysis, and frequently by cataplexy—in other words, a “loss of muscle strength triggered by positive emotions such as laughter,” explains Yves Dauvilliers of Montpellier University Hospital and team leader at the Montpellier Institute of Neurosciences, Inserm, University of Montpellier.
Narcolepsy is an autoimmune disorder with both genetic and environmental causes, whose symptoms are triggered by the destruction of a specific type of neuron—those that produce orexin, also known as hypocretin, a neurotransmitter whose primary role is to promote wakefulness. In narcoleptic patients, 80,000 neurons are destroyed, resulting in a lack of orexin. Consequently, they are unable to maintain a state of wakefulness for long periods.
Patients who claim to be cured
Yves Dauvilliers and his colleagues tested a new treatment developed by Takeda, an orexin receptor 2 agonist—“a molecule that acts like a key similar to orexin and therefore produces the same effects on the body.” While an equivalent treatment had already been tested via intravenous injection, this was the first time it was administered to patients orally. “They were divided into three groups that received doses of 30 mg, 90 mg, or 120 mg of this molecule called TAK-994, and a placebo group , ” explains Yves Dauvilliers. And in terms of improvement, the results were spectacular: “We didn’t just see an improvement in symptoms; for the first time, patients simply felt cured.”
Although the clinical trial had to be halted prematurely due to liver-related side effects in some patients, it nonetheless offers real hope for a cure for all narcoleptics who struggle to stay awake.“We are already working on a new agonist with greater affinity for the orexin receptor 2, which would therefore have fewer side effects,” explains Yves Dauvilliers.
While waiting for this future treatment to become available, the neurologist stresses the importance of early diagnosis of the condition. “It’s important to understand that falling asleep in class when you’re young can be a sign of an underlying condition,” emphasizes Yves Dauvilliers. “Today, on average, it takes eight years to diagnose narcolepsy, and only one-third of patients have a diagnosis—that’s really far too few.”
Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1, Y. Dauvilliers, E. Mignot, R. del Río Villegas, Y. Du, E. Hanson, Y. Inoue, H. Kadali, E. Koundourakis, S. Meyer, R. Rogers, T.E. Scammell, S.I. Sheikh, T. Swick, Z. Szakács, P. von Rosenstiel, J. Wu, H. Zeitz, N.V. Murthy, G. Plazzi, and C. von Hehn. July 27, 2023, N Engl J Med 2023; 389:309-321 DOI: 10.1056/NEJMoa2301940