How Orexin Research is Reshaping Our Understanding of Narcolepsy Type 1

This story is intended for general public information and does not provide medical advice or guidance. Please consult your healthcare provider with any questions regarding its relevance to your health

Sleep could be mistaken for simple rest, but in truth, it is a highly orchestrated biological process — one that repairs tissues, clears debris from the brain, consolidates memories, and helps regulate mood and metabolism¹. When this finely tuned system is chronically disrupted, the consequences can be dramatic. This is certainly the case in narcolepsy, a rare neurological disorder where the boundary between sleep and wakefulness becomes blurred.

Most of us have experienced a "bad night's sleep" that has left us groggy during the day. But imagine if that were your "normal": consistently experiencing disrupted sleep at night and struggling to stay awake during the day. That’s daily life for people living with narcolepsy type 1 (NT1), who must also cope with symptoms like sleep paralysis, hallucinations and sudden muscle weakness usually provoked by strong emotions (known as cataplexy). And if that weren’t troubling enough, people with NT1 can also experience difficulty thinking clearly, remembering, concentrating and paying attention².

First described in medical literature more than a century ago³, the biological cause of NT1 was only decoded in 1999 – when Professors Emmanuel Mignot at Stanford University and Masashi Yanagisawa at the University of Tsukuba – independently and unbeknownst to each other discovered the genetic clues behind the disease. Their research — which would later earn them the prestigious Breakthrough Prize in Life Sciences in 2023— revealed that a previously unknown chemical messenger in the brain called orexin (also known as hypocretin) and its receptor make up part of a system that is central to regulating sleep and wakefulness⁴.

To understand this system, think of receptors as locks embedded on the surface of brain cells called neurons, and think of chemical messengers like orexin as keys designed to fit those locks. When the right key fits into its corresponding lock, it triggers a cascade of biological signals — in this case, promoting wakefulness and preventing the sudden onset of sleep. Without the key, the lock remains inactive, and the system falters.

Mignot, studying narcoleptic dogs, and Yanagisawa, working with genetically modified mice, each found that when orexin signaling was absent or impaired, the brain's ability to sustain wakefulness collapsed. In parallel, Jerome Siegel at University of California, Los Angeles, found evidence that people with NT1 experienced a loss of orexin-producing neurons⁵.

Collectively, these findings not only explained the biology of NT1 but also pointed toward a potential therapeutic path. Leveraging this knowledge, Takeda scientists hypothesized that there could be a way to compensate for the loss of orexin by designing a synthetic (man-made) molecule that could help restore balance to the sleep-wake cycle in people with NT1. Today, researchers at Takeda and elsewhere are testing this very hypothesis. Their findings may also be applicable to other sleep-wake disorders where orexin biology plays a role.

View this video to learn more about the biology of narcolepsy type 1 and the daily symptoms that people experience with this debilitating disease.

Takeda does not have any products approved by any regulatory agencies for use in narcolepsy type 1.

Job Number: C-ANPROM/INT/NSP/0011; DoP: June 2025