French and Japanese scientists win Lasker Prize for narcolepsy breakthrough

Emmanuel Mignot and Masashi Yanagisawa received the Albert Lasker Prize this week for work that fundamentally changed how medicine understands narcolepsy—the neurological condition that strikes people with sudden, irresistible sleep. The two scientists, working independently in the 1990s through entirely different methods, arrived at the same discovery: narcolepsy stems from the absence of a single brain chemical called orexin, also known as hypocretin.

Mignot, a professor at Stanford University School of Medicine, began his investigation convinced that narcolepsy—which he describes as genuinely bizarre—held a genetic explanation. Colleagues thought he was pursuing an impossible path. He spent a decade mapping the genomes of dogs, in which narcolepsy runs in families, searching for the responsible gene. The work finally yielded results in 1999. Around that same period, Yanagisawa, a doctor and biologist at Tsukuba University in Japan, identified orexin itself while investigating what he initially believed was a hunger-related neurotransmitter. When he observed its absence in mice with narcolepsy, the connection became clear. "That was a very dramatic and beautiful convergence of science," Yanagisawa told AFP.

Their findings revealed the precise mechanism at work. In people and mice with narcolepsy, orexin—normally produced by the hypothalamus deep in the brain—is simply not there. In dogs carrying the hereditary form, the molecule exists but cannot function because a genetic mutation has jammed the receptor it needs to activate, like a key that no longer fits its lock. This discovery that narcolepsy had a genetic foundation shook the medical establishment. Sleep research had never been considered a domain for genetics and molecular biology. Before this, scientists studying sleep had only crude tools: they would damage brain tissue and observe what happened. The identification of a genetic root opened entirely new pathways for understanding and treating sleep disorders.

The practical consequences have been profound. After decades of research building on Mignot and Yanagisawa's work, a drug targeting orexin deficiency in Type 1 narcolepsy received approval this year in the United States, China, and Japan. Mignot describes it as transformative. His patients have experienced dramatic improvement. Many had lived with narcolepsy so severe it consumed their lives—they could not pursue hobbies, could not sustain normal activity. "Suddenly they are back to normal," Mignot said. "I have some who started playing hockey or dancing. It gave them back their freedom."

Other medications have also emerged, working through a different mechanism by blocking orexin's stimulating effects, and these are now helping people with insomnia. Yet despite more than three decades since their original work—and despite receiving the Breakthrough Prize in 2023, often called the Oscars of science—fundamental mysteries about sleep remain unsolved. Researchers now understand the mechanics of the transition between sleep and wakefulness, but what actually initiates that shift is still unknown. Yanagisawa calls it "a real mystery."

In narcolepsy specifically, questions persist about why patients lose orexin in the first place. Mignot suspects an autoimmune attack and is currently investigating whether the flu virus might trigger it. There is also the peculiar symptom that defines narcolepsy for many sufferers: sudden sleep onset tied to strong emotion—laughter, surprise, anger. The connection remains unexplained. "Normally, when people find something funny, they get ready to respond with a joke," Mignot observed. "We don't really understand why they fall asleep." The Lasker Prize recognizes work that opened a door. What lies beyond it, sleep science is still learning.