Narcolepsy: Living in balance between sleep and wakefulness. Only 1 in 3 patients is diagnosed.

There are those who struggle every day to stay awake, literally. Those who fear laughter because it might knock them to the ground. Those who live with a body that suddenly shuts down, without warning. This is the daily reality of those suffering from type 1 narcolepsy, a rare and debilitating disease that radically changes the way we live, work, love, and socialize. In Italy, there are approximately 2,000 officially diagnosed cases, but it is estimated that the number of people actually affected is at least three times that. Making diagnosis difficult is the similarity of the symptoms to those of other neurological or psychiatric conditions. The result? Delays in diagnosis, years of clinical misunderstandings, and a quality of life that, in the meantime, deteriorates.

The symptoms

Those with type 1 narcolepsy experience a whole range of symptoms: excessive daytime sleepiness, cataplexy (sudden loss of muscle tone in response to emotion), sleep paralysis, hypnagogic or hypnopompic hallucinations, and profoundly disturbed nighttime sleep. "Type 1 narcolepsy is a disorder that, in the affected individual, impacts 24-hours a day, makes functioning very difficult, and prevents them from leading a healthy and productive life," explains Giuseppe Plazzi , neurologist, coordinator of the Center for Narcolepsy and Sleep Disorders at the IRCCS Institute of Neurological Sciences of the Bellaria Hospital in Bologna, and Professor of Child and Adolescent Neuropsychiatry at the University of Modena and Reggio Emilia. Added to this are anxiety, irritability, relationship difficulties, and a loss of independence.

The 'cataplectic face'

Type 1 narcolepsy significantly impacts the lives of patients. "Whether it presents in young people, with weight gain, the typical 'cataplectic face' and sleep disturbances that affect daytime attention, or when it manifests later in life, with cataplexy, sleep paralysis, hallucinations, nighttime sleep disturbances and daytime sleepiness, potentially causing accidents while driving, at home, or at work," emphasizes Massimo Zenti , President of the Italian Association of Narcoleptics and Hypersomniacs. For example, cataplexy is a truly disabling symptom: it presents with muscle weakness that can start in the face and then involve the upper and lower limbs, causing the person to collapse to the floor. The narcoleptic is aware of what is happening to him, but cannot react because he is completely atonic. Emotions also become a minefield: laughter, surprise, or anger can trigger a cataplexy episode, leaving the body completely atonic but the mind conscious. A suspended, frightening state, difficult to explain and understand.

The role of research

As a rare disease, research is essential for patients. In Bologna, the Narcolepsy Center, directed by neurologist Giuseppe Plazzi, is a national and international reference point. Over 1,000 patients are studied and treated here, more than 70% of whom come from outside the region. The center is part of the European scientific network and has long-standing collaborations with leading research institutions such as Stanford and Montpellier. Alongside the clinical practice, there is also a significant commitment to university education and psychosocial research: understanding how narcolepsy impacts learning, school life, and relationships is a fundamental part of its work. In 2024, Aps Nait – Gruppo Narcolepsy Italiano (Italian Narcolepsy Group) was founded, a network uniting Italian specialists and centers to improve the clinical and scientific management of the disease. Its goal: to build a solid database, promote training, organize events with patient associations, and make those living with this invisible condition feel less alone.

A molecule under study

And today, for the first time, there is concrete hope that science is about to truly change things. The New England Journal of Medicine has published the results of the Phase 2b study of oveporexton, a molecule that directly targets the cause of narcolepsy: the lack of orexin, a neurotransmitter that regulates the sleep-wake cycle. "Oveporexton is a synthetic orexin receptor 2 agonist, and therefore aims to replace the orexin deficiency that causes this condition," says Plazzi. "The data supporting the Phase 2b study demonstrated clinically significant improvements across the entire spectrum of symptoms affecting patients, on objective and subjective measures of excessive daytime sleepiness (EDS), on the reduction of cataplexy episodes, on disease severity, and on quality of life at all doses tested compared to placebo, during the eight weeks of treatment."

Efficacy data

The data are promising. Oveporexton showed significant improvements in all key symptoms: reduced drowsiness, a dramatic decrease in cataplexy episodes, greater emotional stability, and improved quality of life. The therapy was effective, safe, and well-tolerated. The Bologna Center played a leading role in the study, enrolling the largest number of patients. "We finally have a tool that doesn't just contain symptoms, but addresses them at their root," explains Plazzi. If the Phase 3 data (expected by the end of 2025) confirm what we observed, we could be facing a radical turning point."

A day without limits

Massimo Zenti, president of the Italian Association of Narcoleptics and Hypersomniacs, confirms how this therapy has already changed the lives of those who have tried it: "Many patients have been able, for the first time, to live a whole day without symptoms, without paralyzing fatigue, and without the side effect of fogginess. It's a revolution." Those suffering from type 1 narcolepsy don't ask for miracles. They ask to be able to live a normal life. To go to work without fear of falling asleep. To drive. To engage in a conversation without fear of falling to the floor. To experience joy without fear. Thanks to research, that day could be much closer.