Breakthrough Prize is awarded to scientists who uncovered the cause of narcolepsy.

Emmanuel Mignot and Masashi Yanagisawa were awarded the 2023 Breakthrough Prize in life sciences for discovering the chemical mechanisms in the brain that induce narcolepsy.

The 2023 Breakthrough Prize was awarded to Masashi Yanagisawa and Emmanuel Mignot for their discovery of the cause of narcolepsy.

Masashi Yanagisawa and Emmanuel Mignot were the recipients of the Breakthrough Prize.

Emmanuel Mignot and Masashi Yanagisawa have been awarded the 2023 Breakthrough Prize in Life Sciences for finding the origin of narcolepsy, a lifelong illness characterised by sudden sleep attacks and excessive tiredness during the day.

Each year, the Breakthrough Prize grants $15 million in five prizes to the world's leading researchers in physics, mathematics, and the biological sciences.

Emmanuel Mignot of Stanford University in California and Masashi Yanagisawa of the University of Tsukuba in Japan separately found the underlying mechanism of narcolepsy.

Mignot and his colleagues began interbreeding narcoleptic dogs in the 1980s in an effort to find genes associated with the disorder. “When I began doing this, many thought I was insane because the human genome had not yet been sequenced,” explains Mignot. “In fact, it was so insane that it took me a decade, but it paid off.”

The gene identified by his team encoded for two brain membrane receptors. Membrane receptors are located on the cell membrane and detect chemicals outside the cell. Certain chemicals activate receptors, initiating a cascade of responses that frequently result in behavioural changes in an organism. Mignot was unsure of the function of these newly discovered receptors, let alone the compounds to which they responded.

Simultaneously, Yanagisawa and his colleagues were attempting to determine the functions of hundreds of receptors by identifying the peptides that triggered them. They accomplished this by collecting peptide mixtures from animal brains and refining them until they could determine which specific peptides activate a particular receptor. Their first hit was the receptor that Mignot was also studying, which they discovered responded to two previously unidentified peptides, orexin-A and orexin-B.

Then, Yanagisawa and his team blocked the gene that produced orexin in mice and saw that usually nocturnal mice experienced recurrent bouts of sleep at night, akin to narcolepsy. When orexin was injected into the mice's brains at night, they were able to remain awake.

Not only did these studies disclose the membrane receptor implicated in narcolepsy, but also the two kinds of orexin that usually bind to this receptor to generate wakefulness. Additional studies confirmed that narcoleptics do not make orexin.

According to Yanagisawa, this was a dramatic and exhilarating convergence of two laboratories coming from very different directions.

Recent research by Mignot suggests that narcolepsy may be an autoimmune disorder in which the body's immune system assaults and destroys orexin-producing cells in the brain.

The Breakthrough Prize was granted to Mignot and Yanagisawa because their discovery has advanced our understanding of sleep and inspired the development of novel medications to treat narcolepsy, which is estimated to affect approximately 1 percent of the world's population. While none have been authorised as of yet, numerous are undergoing clinical trials at various stages. “If all goes well, a clinically available pharmacological treatment will be ready within three or four years,” adds Yanagisawa.

This year, two further Breakthrough Prizes in the life sciences were awarded to Demis Hassabis and John Jumper for the invention of AlphaFold and to Clifford Brangwynne and Anthony Hyman for the discovery of a basic mechanism in cellular organisation.

In mathematics, Daniel Spielman received for his contributions to theoretical computer science, while Charles Bennett, Gilles Brassard, David Deutsch, and Peter Shor shared the fundamental physics prize for their work in quantum information.

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