(Mignot compared the biology of narcolepsy to that of Type I diabetes, in which the body’s immune system destroys insulin-producing cells in the pancreas.) Further work from his lab would show that human narcolepsy is an autoimmune disorder in which some 70,000 orexin-producing neurons in the hypothalamus are destroyed by the body’s own immune system. The next year, Mignot demonstrated that orexin, which promotes wakefulness and blocks REM sleep, was absent in the brains of human patients with narcolepsy. Around the same time, in parallel work in mice, Yanagisawa had come to the same conclusion. Mignot published his findings, showing that narcolepsy was caused by the disruption of the orexin system in the brain in Cell in 1999. The gene turned out to control a receptor for a sleep-modulating neurotransmitter, commonly known today as orexin, that had been recently discovered by fellow Stanford Medicine sleep researcher, Luis de Lecea, PhD, and separately by Yanagisawa in Japan. I was trained as a psychiatrist, but I became a geneticist,” he said. “Probably it was a little bit of naivete because I was not a geneticist. It was a bold approach at the time, one year before the Human Genome Project was even underway. In 1989, he embarked on a project to find the gene that causes narcolepsy in dogs. Despite not having a faculty position or grants to support his work, he resigned from his professorship in France and continued his research at Stanford Medicine. The experience convinced Mignot that narcolepsy was a tractable problem that could be understood and solved - he was hooked. Working in the lab of the late William Dement, MD, PhD, who was known as the father of sleep medicine, Mignot studied the drug modafinil and showed that it worked in a manner similar to amphetamines by increasing dopamine levels in the brain. Mignot’s interest in studying narcolepsy began in 1986, when he convinced the French government that, as part of his mandatory military service, he should be sent to Stanford Medicine to study a drug for narcolepsy that had been developed by a French company. Mignot, who so deeply deserves this recognition.” “Groundbreaking, life-changing research like this is what we strive to enable every day at Stanford. Mignot and his colleagues led the way to a discovery that would change the lives of millions of people around the world struggling with narcolepsy’s terrible and unpredictable effects,” said Marc Tessier-Lavigne, president of Stanford University. “Through unflinching curiosity and persistence, Dr. The disorder, which affects about 1 in 2,000 people, is usually diagnosed between childhood and young adulthood. People with narcolepsy contend with sudden bouts of sleepiness and muscle weakness, known as cataplexy, that can be triggered by strong emotional excitement. Narcolepsy is a neurological disorder characterized by extreme sleepiness and rapid transition into REM sleep, the sleep phase in which dreams occur. Mignot has dedicated his career to understanding and treating narcolepsy and other sleep disorders. Mignot forever changed the field of sleep medicine and, in doing so, opened the door for more discoveries across a variety of neurodegenerative diseases.” Mignot’s research not only unearthed the protein at the center of this mystery but also led to effective treatments and therapies for people suffering from the condition. “For so many years, the neurological mechanisms that cause narcolepsy were a complete mystery to the medical community,” said Lloyd Minor, MD, dean of the Stanford School of Medicine. Nearly $16 million was awarded this year. The Breakthrough Prize recognizes top scientists for their game-changing discoveries in the fields of life sciences, fundamental physics and mathematics. “When I started studying narcolepsy, people thought it was very rare. “I became interested in narcolepsy because I thought it was a key to understanding sleep, and because it had this human dimension of trying to help patients with this disease that nobody cared about,” Mignot said. He will share the $3 million prize with Masashi Yanagisawa, MD, PhD, of the University of Tsukuba for discovering the causes of narcolepsy and paving the way for new treatments for sleep disorders. Emmanuel Mignot, MD, PhD, the Craig Reynolds Professor of Sleep Medicine, is the winner of a 2023 Breakthrough Prize in Life Sciences.
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