A major step forward in the treatment of narcolepsy
While difficulty staying awake may seem trivial, it is actually the main 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), headed by Yves Dauvilliers, is conducting cutting-edge research on this disease. The neurologist and his colleagues, in partnership with Takeda Laboratories, have just conducted a groundbreaking study on a promising treatment. Their work was published in the New England Journal of Medicine on July 27, 2023.
Nearly 20,000 people in France suffer from narcolepsy, a condition that usually 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. Drowsiness can sometimes be accompanied by weight gain, hallucinations, sleep paralysis, and frequently cataplexy, or " loss of muscle strength linked to 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 disease of genetic and environmental origin whose symptoms are caused by the destruction of a particular type of neuron, those that synthesize orexin, also known as hypocretin, a neurotransmitter whose main role is to stimulate wakefulness. In narcoleptic patients, 80,000 neurons are destroyed, resulting in a lack of orexin. As a result, they are unable to remain awake for long periods of time.
Patients who report being cured
Yves Dauvilliers and his colleagues tested a new treatment developed by Takeda Laboratories, an orexin receptor 2 agonist, "a molecule that acts like a key similar to orexin and therefore has the same effects on the body." Although an equivalent treatment had already been tested by intravenous injection, this was the first time it had been given 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 one group received a placebo , " 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 stopped prematurely due to liver side effects in some patients, it nevertheless offers real hope of a cure for all narcoleptics who struggle to stay awake. "We are already working on a new agonist with greater affinity for the orexin 2 receptor, which should therefore have fewer side effects," explains Yves Dauvilliers.
While waiting for this future treatment to arrive, the neurologist emphasizes the importance of early diagnosis of the disease. "It is important to understand that sleeping in class when you are young can reveal an underlying disease," insists Yves Dauvilliers. Today, it takes an average of eight years to diagnose narcolepsy, and only one-third of patients are diagnosed, which is 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