Bibliography
 | This section needs expansion. You can help by adding to it. (March 2015) |
Dr. Mignot has written many published works in the field of sleep medicine. [12] [13]
Emmanuel Mignot | |
|---|---|
| Born | 1959 (age 64–65) Paris, France |
| Education | Université Pierre and Marie Curie Necker-Enfants Malades, Université René Descartes École Normale Supérieure |
| Known for | Work on narcolepsy |
| Medical career | |
| Profession | Medical doctor |
| Institutions | Stanford Center for Sleep Sciences and Medicine |
| Sub-specialties | Psychiatry |
| Research | Sleep disorders |
Emmanuel Mignot (born 1959 in Paris) is a sleep researcher and director of the Stanford Center for Sleep Sciences and Medicine, at Stanford University. Dr. Mignot is an authority on sleep research and medicine, and is mostly known for his work on narcolepsy. He is the Craig Reynolds Professor of Sleep Medicine at Stanford Medical School, Stanford University. [1]
Dr. Emmanuel Mignot completed his Science Doctorate in Molecular Pharmacology at the Université Pierre and Marie Curie and went to medical school at Necker-Enfants Malades, Université René Descartes, with subspecialisation in Psychiatry. Dr. Mignot is a former student of École Normale Supérieure (Ulm).
Following a postdoctoral fellowship at the Stanford Sleep Center, Mignot believed that understanding narcolepsy could lead to breakthrough in new understanding of sleep. He was appointed assistant professor of psychiatry and behavioral sciences at Stanford University in 1993, professor in 2001 and director of the Center for Sleep Sciences and Medicine in 2011, succeeding William C. Dement. Trained as a pharmacologist, he first deciphered the mode of action of modafinil, amphetamines, and antidepressants on narcolepsy symptoms, [2] work that was done in close collaboration with Dr. Seiji Nishino.
Starting in 1990, he isolated the gene causing canine narcolepsy in doberman and Labrador dogs. Ten years later, this led to the discovery that mutations in the hypocretin (orexin) receptor 2 cause canine narcolepsy, [3] and that human narcolepsy was caused by an immune mediated destruction of the hypocretin (orexin) producing cells in the brain [4] Parallel work performed by Mashashi Yanagisawa, Christopher Stinton and colleagues subsequently showed that hypocretin (orexin) deficient mice also have narcolepsy. [5]
The autoimmune destruction of hypocretin (orexin) neurons in the hypothalamus was later shown by Han and Mignot to be at least partially precipitated by influenza A infections, notably the H1N1 2009 pandemic strain, [6] complementing findings made in Northern Europe following the H1N1 Pandemrix vaccination campaign. [7]
Dr. Mignot identified genetic factors predisposing to human narcolepsy, such as human leukocyte antigen HLA DQB1*06:02 and other genes [8] and isolated the gene causing the methylopathy Autosomal Dominant Cerebelar Ataxia, Deafness and Narcolepsy (ADCA-DN), DNMT1. [9]
Dr. Mignot has received numerous research grants and honors, including National Sleep Foundation and National Institute of Health Research Awards, Howard Hughes Medical Institute Investigator and McKnight Neuroscience awards, the Narcolepsy Network [10] professional service award, the Drs. C. and F. Demuth 11th Award for Young Investigators in the Neurosciences, the WC Dement Academic Achievement Award in sleep disorders medicine, the CINP and ACNP awards in neuropharmacology and the Jacobaeus prize. He is an elected member of the Association of American Physicians and of the Institute of Medicine of the National Academy of Sciences. He is the co-author of more than 200 original scientific publications, and he serves on the editorial board of scientific journals in the field of sleep and biology research. Dr. Mignot is an active member of several professional and governmental organizations. He has been past president of the Sleep Research society, chair the National Center on Sleep Disorders Research Advisory board of the National institutes of Health and chair of the Board of Scientific Counselors of the National Institute of Mental Health. For 2023 he was awarded the Breakthrough Prize in Life Sciences for discovering that narcolepsy is caused by the loss of a small population of brain cells that make a wake-promoting substance, paving the way for the development of new treatments for sleep disorders. [11]
| | This section needs expansion. You can help by adding to it. (March 2015) |
Dr. Mignot has written many published works in the field of sleep medicine. [12] [13]
A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Sleep disorders are frequent and can have serious consequences on patients' health and quality of life. Polysomnography and actigraphy are tests commonly ordered for diagnosing sleep disorders.
Orexin, also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. It exists in the forms of orexin-A and orexin-B. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone, is caused by a lack of orexin in the brain due to destruction of the cells that produce it.
Wakefulness is a daily recurring brain state and state of consciousness in which an individual is conscious and engages in coherent cognitive and behavioral responses to the external world.
Cataplexy is a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, or terror. Cataplexy affects approximately 20% of people who have narcolepsy, and is caused by an autoimmune destruction of hypothalamic neurons that produce the neuropeptide hypocretin, which regulates arousal and has a role in stabilization of the transition between wake and sleep states. Cataplexy without narcolepsy is rare and the cause is unknown.
In medicine, a biomarker is a measurable indicator of the severity or presence of some disease state. It may be defined as a "cellular, biochemical or molecular alteration in cells, tissues or fluids that can be measured and evaluated to indicate normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention." More generally a biomarker is anything that can be used as an indicator of a particular disease state or some other physiological state of an organism. According to the WHO, the indicator may be chemical, physical, or biological in nature - and the measurement may be functional, physiological, biochemical, cellular, or molecular.
The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity, and eating disorders.
Timeless (tim) is a gene in multiple species but is most notable for its role in Drosophila for encoding TIM, an essential protein that regulates circadian rhythm. Timeless mRNA and protein oscillate rhythmically with time as part of a transcription-translation negative feedback loop involving the period (per) gene and its protein.
Orexin receptor type 1 (Ox1R or OX1), also known as hypocretin receptor type 1 (HcrtR1), is a protein that in humans is encoded by the HCRTR1 gene.
Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene. It should not be confused for the protein CD200R1 which shares the alias OX2R but is a distinct, unrelated gene located on the human chromosome 3.
Pandemrix is an influenza vaccine for influenza pandemics, such as the 2009 flu pandemic. The vaccine was developed by GlaxoSmithKline (GSK) and patented in September 2006.
Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM sleep. The pentad symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep related hallucinations, sleep paralysis, disturbed nocturnal sleep (DNS) and cataplexy. There are two recognized forms of narcolepsy, narcolepsy type 1 and type 2. Narcolepsy type 1 (NT1) can be clinically characterized by symptoms of EDS and cataplexy, and/or will have CSF orexin levels of less than 110 pg/ml. Cataplexy are transient episodes of aberrant tone, most typically loss of tone, that can be associated with strong emotion. In pediatric onset narcolepsy, active motor phenomena are not uncommon. Cataplexy may be mistaken for syncope, tic disorder or seizures. Narcolepsy type 2 (NT2) does not have features of cataplexy and CSF orexin levels are normal. Sleep related hallucinations, also known as hypnogogic and hypnopompic are vivid hallucinations that can be auditory, visual or tactile and may occur independent of or in combination with an inability to move. People with narcolepsy tend to sleep about the same number of hours per day as people without it, but the quality of sleep is typically compromised. Narcolepsy is a clinical syndrome of hypothalamic disorder, but the exact cause of narcolepsy is unknown, with potentially several causes. A leading consideration for the cause of narcolepsy type 1 is that it is an autoimmune disorder. Proposed pathophysiology as an autoimmune disease suggest antigen presentation by DQ0602 to specific CD4+ T cells resulting in CD8+ T-cell activation and consequent injury to orexin producing neurons. Familial trends of narcolepsy are suggested to be higher than previously appreciated. Familial risk of narcolepsy among first degree relatives is high. Relative risk for narcolepsy in a first degree relative has been reported to be 361.8. However, it is important to note that there is a spectrum of symptoms found in this study, including asymptomatic abnormal sleep test findings to significantly symptomatic.
Eugeroics, also known as wakefulness-promoting agents and wakefulness-promoting drugs, are a class of drugs that promote wakefulness and alertness. They are medically indicated for the treatment of certain sleep disorders including excessive daytime sleepiness (EDS) in narcolepsy or obstructive sleep apnea (OSA). Eugeroics are also often prescribed off-label for the treatment of EDS in idiopathic hypersomnia. In contrast to classical psychostimulants, such as methylphenidate and amphetamine, which are also used in the treatment of these disorders, eugeroics typically do not produce marked euphoria, and, consequently, have a lower addictive potential.
Suvorexant, sold under the brand name Belsomra, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance in adults. Suvorexant helps with falling asleep faster, sleeping longer, being awake less in the middle of the night, and having better quality of sleep. Its effectiveness is modest, and is similar to that of other orexin antagonists, but is lower than that of benzodiazepines and Z-drugs. Suvorexant is taken by mouth.
An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one (selective orexin receptor antagonist or SORA) or both (dual orexin receptor antagonis or DORA) of the orexin receptors, OX1 and OX2. Medical applications include treatment of sleep disorders such as insomnia.
Thomas S. Kilduff is an American neuroscientist and the director of SRI International's Center for Neuroscience. He specializes in neurobiology related to sleep and wakefulness, and was involved in the discovery of hypocretin, a neuropeptide system that is highly involved in wakefulness regulation.
Danavorexton is a selective orexin 2 receptor agonist. It is a small-molecule compound and is administered intravenously. The compound was found to dose-dependently produce wakefulness to a similar degree as modafinil in a phase 1 clinical trial. As of March 2021, danavorexton is under development for the treatment of narcolepsy, idiopathic hypersomnia, and sleep apnea. It is related to another orexin receptor agonist, firazorexton (TAK-994), the development of which was discontinued for safety reasons in October 2021.
Seiji Nishino is a Japanese neuroscientist and writer. He is a professor emeritus of psychiatry and behavioral sciences at the Stanford University. He is also the director of Stanford Center for Sleep Sciences and Medicine.
Firazorexton (INNTooltip International Nonproprietary Name; development code TAK-994) is an experimental orexin 2 (OX2) receptor agonist first described in a 2019 patent filed by Takeda Pharmaceutical Company.
Masashi Yanagisawa is a Japanese-American molecular biologist and physician, famous for his discovery of the hormone endothelin and the neuropeptide orexin, the absence of which is the cause of narcolepsy. He is currently the Director of the International Institute for Integrative Sleep Medicine, University of Tsukuba, and an adjunct professor at the Department of Molecular Genetics, University of Texas Southwestern Medical Center.
Pediatric narcolepsy refers to conditions of narcolepsy during childhood and adolescence. In a pediatric setting, people with narcolepsy still exhibit the classical tetrad symptoms of narcolepsy, and thus is possible for both type 1 and type 2 narcolepsy to develop in adolescence.
