Heidi Ledford By learning from patients who nod off unexpectedly during the day, researchers have pinpointed a chemical that could help people who can't sleep at night. One out of every 10 people in the United States suffers from chronic insomnia, making for a big sleeping-pill market. The most popular pills work by strengthening the effects of a brain chemical that slows the nervous system and promotes relaxation. But these drugs can also carry unpleasant side effects, including memory loss and grogginess the next day. The race for a better sleeping pill is still on. Now, a new approach targets brain hormones called orexins. Orexins are known to be linked to sleepiness; patients with a sleeping disorder called narcolepsy have low levels of these hormones and are chronically sleepy during the day, sometimes falling asleep on the job or while driving. The new chemical, known as ACT-078573, blocks the action of orexins. When given to dogs, rats and humans, it decreased alertness in all three species, while shortening the time it took for them to fall asleep. François Jenck, of the Swiss biotech company Actelion Pharmaceuticals in Allschwil, and his colleagues report the findings in the journal Nature Medicine1. Orexins aren't an obvious target for developing new sleeping pills. Narcoleptics suffer not only from sleepiness, but also from sudden loss of muscle tone that, in extreme cases, can cause them to collapse and remain frozen - fully conscious - for minutes at a time. Laughter often triggers a collapse in human narcoleptics, whereas narcoleptic dogs can crumple from the thrill of dinnertime or being let loose to play in the yard. "They get excited and run out the door and just go 'thump'," says Jerome Siegel, a sleep researcher at the University of California, Los Angeles. ©2007 Nature Publishing Group

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming; Chapter 13: Homeostasis: Active Regulation of the Internal Environment
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep; Chapter 9: Homeostasis: Active Regulation of the Internal Environment
Link ID: 9893 - Posted: 06.24.2010

Paradoxically, a single MHC class II allele, HLA-DQ0602, confers susceptibility to narcolepsy but prevents development of type I diabetes. Clinical immunologist Lars Fugger and structural biologist Yvonne Jones, both at Oxford University, have compared the crystal structure of the allele with those of two similar MHC molecules that respectively predispose to type 1 diabetes and protect against narcolepsy.1 They have identified unique features of several pockets within the peptide-binding groove of HLA-DQ0602 that could explain the contradiction through differential influences on T-cell stimulation. In particular, says Fugger, the extra large P4 pocket selectively accommodates a candidate auto-antigenic peptide that might stimulate autoreactive T cells in narcolepsy, a potential autoimmune disorder. For diabetes, the unusual stability of the P9 pocket could promote development of regulatory T cells able to actively suppress disease-causing T cells. "In many ways," he adds, "I would say that narcolepsy and diabetes could be mirrors of each other." © 2004, The Scientist LLC,

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep
Link ID: 5126 - Posted: 06.24.2010

Copyright © 2002 AP Online By LAURAN NEERGAARD, AP Medical Writer WASHINGTON - The notorious date-rape drug GHB won government approval Wednesday to treat a rare but dangerous complication of the sleep disorder narcolepsy - but it will be sold under some of the most severe restrictions ever imposed on a medicine. The Food and Drug Administration approval puts the chemical in a peculiar position. Throughout the 1990s, the government cracked down on illegal use of GHB - abused as a party drug, sex and athletic enhancer and - because it can knock people out - a date-rape drug. Several dozen deaths are blamed on the chemical's abuse. Now the maker of the only FDA-approved version, Orphan Medical Inc., will have to balance how to get GHB to the relatively few patients who qualify while keeping it from falling into the wrong hands. Copyright © 2001 Nando Media

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming; Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep; Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 2327 - Posted: 06.24.2010

A Mayo Clinic study reports that narcolepsy, a sleep disorder, is more common in men and originates in their 20s. The study, which appeared in a recent edition of the journal Sleep, also found that narcolepsy without cataplexy -- a sudden loss of muscle tone -- is an important subgroup, warranting further study. Narcolepsy is a sleep disorder associated with excessive daytime sleepiness, involuntary daytime sleep episodes, disturbed nocturnal sleep and cataplexy (weakness with emotions such as laughter). Narcolepsy affects over 100,000 people in the United States. Copyright © 1995-2002 ScienceDaily Magazine

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep
Link ID: 1977 - Posted: 06.24.2010

About 50,000 people have been diagnosed with narcolepsy in the U.S, but there may be as many as 2.4 million people unknowingly living with it. Narcolepsy causes excessive daytime sleepiness, fatigue and even sudden muscular weakness, known as cataplexy. Here, six men and women speak about living with narcolepsy. Copyright 2009 The New York Times Company

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep
Link ID: 13214 - Posted: 08.27.2009

Scientists have uncovered genetic evidence suggesting the sleep disorder narcolepsy is linked to a fault in the immune system's "foot soldier" cells. It suggests these T-cells may cause the condition by attacking cells in the sleep centres of the brain. Narcolepsy, which causes extreme daytime sleepiness and sudden muscle weakness, has previously been linked to a malfunctioning immune system. The Stanford University research appears in the journal Nature Genetics. Narcolepsy is a mysterious, uncommon condition that can be very distressing for those who have it. It can trigger "sleep attacks" without any warning during any normal activity. In addition, some people can experience "cataplexy", where strong emotions such as anger, surprise, or laughter can trigger an instant loss of muscle strength, which, in some cases, can cause collapse. There is currently no cure for narcolepsy, only ways to minimise symptoms such as taking frequent, brief naps evenly spaced throughout the day. The condition has previously been linked to depletion of cells deep in the regulatory regions of the brain. But lead researcher Dr Emmanuel Mignot said while previous research had only suggested a link with a fault in the immune system, the latest study provided firm evidence. The Stanford team carried out an extensive genetic analysis to identify specific areas of the genome which appeared to be linked to the condition. They pinpointed three specific genetic variants in the same gene in people with European and Asian ancestry that appeared to be associated with an increased susceptibility for narcolepsy. The gene in question plays a key role in the functioning of an important receptor used by T-cells to recognise foreign proteins in the body. (C)BBC

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming; Chapter 15: Emotions, Aggression, and Stress
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep; Chapter 11: Emotions, Aggression, and Stress
Link ID: 12822 - Posted: 05.05.2009

Genetic research could shed light on what is happening in people with the mysterious sleep disorder narcolepsy. The condition causes extreme daytime sleepiness, and sudden muscle weakness. Japanese researchers found a genetic variant linked to a much higher risk of narcolepsy, publishing their results in the journal Nature Genetics. It is linked to genes involved in regulating sleep, and the scientists say their finding could help unravel narcolepsy's causes. The condition is an uncommon and distressing one - people with it can suffer "sleep attacks" without any warning during any normal activity. In addition, some people can experience "cataplexy", where strong emotions such as anger, surprise, or laughter can trigger an instant loss of muscle strength, which, in some cases, can cause collapse. The causes are still not completely clear, although some scientists believe they revolve around a shortage of a chemical called hypocretin which sends signals to the brain about sleeping and waking up. There is strong evidence that the condition can run in families, so the University of Tokyo team are looking for the genetic differences which may be involved. They looked at the genetic code of hundreds of volunteers, some with narcolepsy, some without, to look for differences. The variant they found was linked to an 79% higher chance of narcolepsy in Japanese people, and a 40% increased chance in other ethnic groups. It is found close to two genes, CPT1B, and CHKB, which have already been singled out as candidates for involvement in the disorder - as they both have a role in regulating sleep. (C)BBC

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep
Link ID: 12086 - Posted: 09.29.2008

A chemical found naturally in the brain could be used to treat the sleep disorder narcolepsy, US scientists say. Researchers at the University of Texas said injecting a chemical called orexin stopped symptoms in mice with narcolepsy. They found the treatment made the mice more alert and reduced other narcoleptic symptoms, such as muscle weakness, called cataplexy. The study appeared in the Proceedings of the National Academy Sciences. Dr Masashi Yanagisawa, professor of molecular genetics, and colleagues studied genetically modified mice which lacked the ability to naturally produce orexin. Orexin are small chains of molecules, produced by nerve cells in the area of the brain called the hypothalamus. (C) BBC

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep
Link ID: 5143 - Posted: 03.16.2004

New Haven, Conn. -- A Yale researcher has received a $1.4 million grant to study a neurotransmitter whose loss in the brain is believed responsible for narcolepsy, an often misunderstood disease marked by an uncontrollable desire to sleep. "It's profoundly debilitating," said Anthony van den Pol, professor of neurosurgery at Yale School of Medicine . "For example, narcoleptics may go to work and, despite their best intentions to the contrary, spontaneously fall asleep, raising the ire of their employer. Then at night they may have trouble sleeping, and may suffer from hallucinations when falling asleep or waking." Van den Pol's laboratory, in collaboration with colleagues at Stanford and the Scripps Research Institute, first described the hypothalamic neurotransmitter, hypocretin, in 1998. Later studies showed that patients with narcolepsy did not have any neurons in the brain to make hypocretin. More recently, van den Pol and other researchers also found that hypocretin appears to be linked to pain modulation in the spinal cord.

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming; Chapter 8: General Principles of Sensory Processing, Touch, and Pain
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep; Chapter 5: The Sensorimotor System
Link ID: 1509 - Posted: 02.09.2002

CHAPEL HILL - A brain protein linked to narcolepsy, the sudden, uncontrollable and inexplicable onset of sleep, helps regulate bodily sensations . Exactly how that protein, hypocretin-2, is involved in narcolepsy remains unclear. Indications are that people and animals exhibiting narcoleptic symptoms are deficient in this protein or the molecular receptor to which it attaches. But the new findings by neuroscientists at the University of North Carolina at Chapel Hill and Yale University may open a door to the answer. Their report is the cover story for the January 15 issue of the Journal of Physiology. According to Dr. Edward R. Perl, professor of cell and molecular physiology at UNC-Chapel Hill School of Medicine and the report's corresponding author, hypocretin peptides are distributed widely throughout the brain. They arise from part of the hypothalamus, a region prominently involved in regulation of the autonomic nervous system, endocrine activity, and mood and motivational states. Recently, these proteins have been implicated in the regulation of behaviors associated with arousal such as feeding and sleep.

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming; Chapter 13: Homeostasis: Active Regulation of the Internal Environment
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep; Chapter 9: Homeostasis: Active Regulation of the Internal Environment
Link ID: 1301 - Posted: 01.11.2002

By DAVID TULLER Robert Cloud, a lawyer in Cincinnati, has fallen asleep while talking to clients, while eating dinner, even while meeting with a judge. Mr. Cloud, 58, has suffered for much of his adult life from narcolepsy, a little-understood sleep disorder that afflicts as many as 100,000 to 200,000 Americans. People with the condition are prone to sudden, uncontrollable attacks of intense sleepiness. They feel exhausted most of the time, and many also experience cataplexy, brief episodes of loss of muscle control that may occur for no apparent reason or be brought on by laughter, anger, embarrassment, excitement or other strong emotions, as well as physical exertion and sexual stimulation. Copyright 2002 The New York Times Company

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep
Link ID: 1284 - Posted: 01.08.2002

Emma Young, San Diego
The devastating sleep disorder narcolepsy could be the result of a sufferer's immune system attacking key cells in the brain, say US scientists. Jerry Siegel at the University of California, Los Angeles and his team gave commonly used immune system suppressants to dogs with a genetic mutation that makes them develop narcolepsy. They found that the onset of the disease was dramatically delayed. Furthermore, when symptoms did appear, they were also much less severe. "The immunosuppressants in dogs produced a reduction in symptoms that is quite remarkable," Siegel says. "It is quite likely that a similar treatment could be effective in humans if we could detect symptoms at an early stage." © Copyright Reed Business Information Ltd.

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep
Link ID: 1012 - Posted: 11.17.2001

Narcolepsy
The incurable sleep disorder, narcolepsy, has long mystified scientists. But recently, several discoveries culled from animal research indicate that molecular brain malfunctions may participate in the development of the ailment. The new insights are focusing the search for targeted human treatments for narcolepsy as well as other types of sleeping problems. Dramatically drowsy during calculus class? Maybe it's the monotone teacher, an overdose of David Letterman or, perhaps, narcolepsy. This brain disorder, which afflicts an estimated 200,000 Americans, is marked by an uncontrollable, overwhelming desire to sleep during the day. The attacks can occur at any time, even in the middle of a conversation about yesterday's homework.

Related chapters from BN: Chapter 14: Biological Rhythms, Sleep, and Dreaming
Related chapters from MM:Chapter 10: Biological Rhythms and Sleep
Link ID: 363 - Posted: 10.20.2001