Sleep is one of the foundational pillars of animal existence. Groundbreaking research by Emmanuel Mignot (Stanford University School of Medicine) and Masashi Yanagisawa (University of Tsukuba) transformed our understanding of how we maintain wakefulness. The 2026 Albert Lasker Basic Medical Research Award honours their work in mice, rats and dogs, that sparked a revolution in sleep science and holds the potential to help millions of people around the world get better rest.
Key messages:
- The 2026 Lasker Basic Medical Research Award honours Emmanuel Mignot (Stanford University) and Masashi Yanagisawa (University of Tsukuba) for discovering the brain chemical orexin and its role in causing narcolepsy.
- Orexin is a brain signaling molecule that regulates wakefulness; when the orexin system fails – whether from a missing peptide or a mutated receptor – animals experience sudden, uncontrollable sleep attacks.
- Emmanuel Mignot identified the gene responsible for narcolepsy in dogs in 1999, discovering that dobermans and labradors with inherited narcolepsy carried mutations in the same orexin receptor gene that Masashi Yanagisawa had independently linked to sleep regulation in rats – a convergence that helped establish orexin's central role in narcolepsy.
- In humans, narcolepsy is generally caused by an autoimmune attack, often triggered by infections such as influenza.
- Narcolepsy affects around 1 in 2,500 people worldwide with 30,000 sufferers in the UK alone, and the discovery of orexin has led directly to new treatments, including orexin receptor-blocking drugs for insomnia.
- The first orexin receptor-activating drug for narcolepsy, oveporexton (Orzeyful™) by Takeda, received FDA approval in August 2026, marking a major treatment milestone stemming from this research.
Deciphering “orphan” brain receptors
In the 1990s, scientists were only beginning to grasp the full scope of how the brain communicates through neurotransmitters. Before then, brain receptors were classified strictly by how they responded to external drugs. But the rise of new molecular cloning techniques allowed scientists to find the genes for receptors before finding the chemicals that activated them, triggering an explosion of newly discovered receptors. By the early 1990s, the list of these "orphan" receptors kept growing, leaving scientists with structures but no known functions.
Breaking with the previous approach, Yanagisawa, then at UT Southwestern Medical Centre in Dallas, went looking for new therapeutic possibilities by searching for molecules that could activate these orphan receptors. Using rat brains, his team managed to identify two molecules that could activate a pair of receptors in a brain region associated with hunger. Injecting these peptides into the brains of rats caused them to eat. Yanagisawa named the neuropeptides "orexins," after the Greek word orexis, meaning appetite.
Between hunger and sleep
Based on these findings, Yanagisawa and postdoctoral fellow Richard Chemelli engineered mice that lacked orexin, expecting the change would suppress appetite. To their surprise, the orexin-deficient mice ate about the same amount and kept roughly the same body weight as normal mice. But maybe the researchers were missing out on changes in their eating patterns.
Mice are nocturnal, so Yanagisawa decided to observe them at night, when they eat most of their food. He and his trainees set up an infrared camera. One night, Chemelli noticed something strange: a mouse that had been grooming and scampering about suddenly collapsed onto its side. It lay motionless for about a minute – then got up and went back to what it was doing.
Suspecting epilepsy, the researchers hooked the mice up to electrodes to see what was happening in their brains. It turned out that during these collapses, the mice's brain waves showed an abrupt shift into rapid eye movement (REM) sleep – the phase in which dreams occur. The mice were falling suddenly and intermittently into sleep, much like what happens in humans with narcolepsy, a condition marked by sudden sleep attacks. Orexin, it turned out, had a far larger effect on sleep than on feeding.
Yanagisawa described these findings in August 1999 – around the same time that another researcher, Emmanuel Mignot, was reporting on an inherited form of narcolepsy in dogs.
The source of narcolepsy in dogs
Mignot had been studying narcolepsy in dobermans and labradors. In these two breeds, the condition was inherited, passed down from parent to pup, and Mignot wanted to identify the gene responsible. But the dog genome hadn't yet been sequenced, or even roughly mapped, which made the search arduous.
It took Mignot nearly a decade, but by 1999, he finally identified a mutated orexin receptor gene as the culprit of narcolepsy in dogs. The gene that he identified was the same receptor gene that Yanagisawa had found earlier in rats. Dobermans and labradors held different genetic errors, each of which resulted in loss of a large and distinct chunk of the receptor.
Through different experimental approaches, Mignot and Yanagisawa had each shown the same thing: without a working orexin receptor, or the signalling peptide itself, animals become prone to sudden sleep fits.
The immune connexion
Mignot didn't stop at dogs. He knew that narcolepsy in humans is rarely inherited within families, so a single genetic mutation couldn't fully explain it. Digging deeper, he found that people with narcolepsy had almost no orexin in their brain fluid, despite carrying entirely normal orexin genes. Something else was affecting orexin levels in the brain.
Mignot went on to uncover an immune connection: infections appeared to raise the risk of developing narcolepsy. A retrospective study by Mignot and colleagues in China revealed a seasonal pattern of onset, with winter infections linked to a higher risk of the disease. The working theory is that microbial triggers can spark an immune attack – potentially aimed directly at orexin-producing neurons – in people whose immune systems are already predisposed to it. In 2023, Mignot identified additional genetic risk factors for narcolepsy, all tied to the immune system.
Towards new treatments for narcolepsy
Animal research was central to both Yanagisawa's and Mignot's work. Together, the two scientists transformed how we understand sleep and narcolepsy, moving the field from classical anatomy into modern molecular biology. They uncovered one of the key molecular mechanisms behind sleep regulation, implicated the immune system in human narcolepsy and, ultimately, pointed the way to new treatments for narcolepsy and other sleep disorders.
In the United States, narcolepsy affects at least 1 in 2,000 people and there are 30,000 sufferers in the UK. Today many of them have Yanagisawa and Mignot to thank for real treatment options. The discovery of orexin has also led to new medicine for those who struggle to sleep : drugs that block orexin receptors, effectively turning off the brain signals that keep you awake, now offer insomnia treatments that avoid many of the downsides of traditional sleep aids. Because these drugs suppress wakefulness rather than force sedation, they produce more natural sleep.
Conversely, chemicals that activate the orexin-2 receptor promise to revolutionise narcolepsy treatment – and may also help people with other conditions involving excessive sleepiness. The first drug in this class, Takeda's oveporexton (marketed as Orzeyful™), received FDA approval in August 2026.
FAQ
What is orexin?
Orexin is a brain signalling molecule (neuropeptide) that regulates wakefulness. It was discovered by Masashi Yanagisawa's team in the 1990s while studying "orphan" brain receptors in mice and rats.
What causes narcolepsy?
Narcolepsy is caused by the loss of orexin signalling in the brain. This can happen through a mutated orexin receptor gene (as found in dogs) or, in most human cases, through an autoimmune attack – often triggered by an infection – that targets the cells that produce orexin.
Who won the 2026 Lasker Basic Medical Research Award, and for what?
Emmanuel Mignot (Stanford University School of Medicine) and Masashi Yanagisawa (University of Tsukuba) won the 2026 Albert Lasker Basic Medical Research Award for discovering orexin and establishing its role in causing narcolepsy.
When was the narcolepsy gene discovered in dogs?
Emmanuel Mignot identified the mutated orexin receptor gene responsible for inherited narcolepsy in dobermans and labradors in 1999 –the same orexin receptor gene that Yanagisawa had linked to sleep regulation in rats.
Is narcolepsy an autoimmune disease?
Although there are genetic triggers to narcolepsy, growing evidence indicates that human narcolepsy can also be autoimmune in nature. Studies have linked external factors such as infections (for example flu) in people who have a genetic predisposition to the destruction of orexin-producing neurons.
How many people are affected by narcolepsy?
In the United States, narcolepsy affects at least 1 in 2,000 people, worldwide it is probably something like 1 in 2,500.
What new treatments has the discovery of the link between orexin and narcolepsy led to?
Drugs that block orexin receptors are now used to treat insomnia. Drugs that activate the orexin-2 receptor are being developed to treat narcolepsy directly – the first of these, Takeda's oveporexton (Orzeyful™), received FDA approval in August 2026.
References :
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Last edited: 30 September 2026 13:12
