Lecture: Emmanuel Mignot
Gene-infection interplay in narcolepsy: an autoimmune disorder affecting hypocretin/orexin neurons
Emmanuel Mignot, Professor of psychiatry and behavioural science at Stanford University of Medicine and Director of the Stanford Center for Sleep Sciences
One of the worlds most prominent sleep and narcolepsy researchers is coming to Sweden to lecture at Karolinska Institutet. Professor Emmanuel Mignot is credited with the discovery that narcolepsy in dogs is attributable to a mutation in a sleep-regulating gene.
Interest in sleep research, especially as regards narcolepsy, has intensified dramatically in Sweden in recent years, owing in part to the mass swine-flu vaccination programme and its links to a rise in narcolepsy amongst children and young adults. The disease normally affects one in 3,000 people and is characterised by a disruption of the sleep-wakefulness pattern, with sudden episodes of sleep and muscle atonia (cataplexy) during the day, and unrestful sleep at night.
Professor Mignot is internationally renowned for having discovered the mutation that causes narcolepsy in dogs. The mutation is in a gene that encodes a neuropeptide called hypocretin (orexin), which is involved in the control of wakefulness.
He is now studying the causes of the human form of narcolepsy, the symptoms of which are caused by a loss of neurons that produce the hypocretin/orexin transmitter. Through his work with large patient groups, he has managed to show that narcolepsy is closely genetically linked to so-called HLA molecules, which play a key part in the immune system by presenting foreign substances to immune cells. This has led to the hypothesis that narcolepsy is an autoimmune disease that could be triggered by infections such as swine flu.
"Our hypothesis is that a combination of a certain HLA variant and a fragment of the H1N1 virus can trigger the immune system," says Professor Mignot. "This sets off an immune reaction that destroys the nerve cells that produce hypocretin/orexin."
Narcolepsy is a disease linked to sleep and neurobiology, neurological diseases such as multiple sclerosis and other autoimmune diseases. Professor Mignots lecture promises therefore to be interesting from a number of perspectives. Sleep and the hypocretin/orexin system is also a topical issue now that companies and scientists are hoping to develop new sleeping drugs based on this substance.
Professor Mignot's lecture will be introduced by Fredrik Piehl, professor of clinical neuroscience at Karolinska Institutet. The moderator is Professor Annika Linde, state epidemiologist at the Swedish Institute for Communicable Disease Control.