Albert Lasker Award for Researchers Who Deciphered the Mechanism of Uncontrollable Sleep

Researchers Emmanuel Mignot and Masashi Yanagisawa have received the prestigious Albert Lasker Award for "fundamental discoveries" that have allowed the elucidation of the mechanisms underlying narcolepsy. The research carried out simultaneously by the two scientists in the 1990s paved the way for new treatments and changed the way sleep is studied, reports AFP. The American award is often considered a possible precursor to the Nobel Prize for Medicine. Mignot, a French researcher who became a professor at Stanford University in California, and Masashi Yanagisawa, a Japanese doctor and biologist, approached the problem of narcolepsy from different directions, almost simultaneously reaching the key to the mechanism of this disorder. Narcolepsy is manifested by sudden and uncontrollable episodes of sleep and can be accompanied by a sudden loss of muscle tone, a phenomenon known as cataplexy.

• Dogs lead research to genetic cause

Fascinated by this disorder, which he considered "super bizarre” and which can manifest itself in both animals and humans, Emmanuel Mignot began researching the causes of narcolepsy after completing his university studies. "Everyone told me it was crazy,” the researcher recalls. "But I really believed in it,” he added. For about a decade, Mignot analyzed the genome of dogs, starting from the observation that narcolepsy could be hereditary. The goal was to identify the gene responsible for the condition. The research yielded results in 1999, when his team identified the gene involved in canine narcolepsy. Around the same time, Masashi Yanagisawa made a discovery that would complement the French researcher's results. Yanagisawa identified orexin, sometimes called hypocretin, a neurotransmitter that the researcher initially thought was related to the feeling of hunger. Later, experiments showed that the absence of orexin causes narcolepsy in mice. "It was a scientific convergence that was both spectacular and magnificent,” Yanagisawa said. The two men's research helped clarify the underlying mechanism of the disease. In humans and mice, the neurotransmitter normally produced in the hypothalamus, at the base of the brain, is missing in narcolepsy. In dogs, orexin is present but cannot perform its function. According to the researchers' explanation, the molecule acts like a "key,” while the "lock” it needs to open is blocked by a genetic mutation.

• A paradigm shift in sleep medicine

The discoveries fundamentally changed the way we approach sleep disorders. "Before our research, sleep had practically never been approached from the perspective of genetics and molecular biology,” recalls Masashi Yanagisawa. In the early 1990s, sleep medicine was still in its infancy, and researchers relied mainly on observing the effects of lesions on sleep in certain regions of the brain. However, the identification of the role of orexin opened up a new direction of research, both for understanding sleep disorders and for developing treatments. After decades of research, the first drug to target orexin deficiency in patients with type 1 narcolepsy was authorized in the summer of 2026 in the United States, China and Japan. "This really changed the data of the problem,” said Emmanuel Mignot, who says he has seen important changes in some of his patients. "Suddenly, they became normal again, some of them even started playing hockey and dancing, it gave them back their freedom,” the researcher said.

• Sleep Research Continues

Orexin is responsible for maintaining wakefulness, and research on this molecule has also led to the development of treatments that block its action. These drugs are currently used to treat insomnia, according to Masashi Yanagisawa.

The researcher believes that research directions can expand as scientists better understand the mechanisms of sleep. Despite the progress made in the last three decades, many questions remain unanswered. Researchers now better understand the mechanisms that allow the transition between wakefulness and sleep, but they do not yet know the mechanism that actually triggers this change. "It is a real mystery," explained the Japanese researcher. Another unknown is the mechanism that triggers narcoleptic episodes. These can occur following strong emotions, such as surprise, laughter or anger. "What's really typical is when people find something funny (...) they're about to tell a joke and suddenly they fall asleep. However, we don't fully understand why this happens." "It is related to sleep," explained Professor Emmanuel Mignot. The discoveries of the two researchers, also awarded the 2023 Breakthrough Prize, have thus transformed narcolepsy from a difficult-to-explain disorder into a field in which biological and genetic mechanisms can be investigated and, increasingly, targeted therapeutically.