Narcolepsy — or “seized by numbness” — is a condition far more common that people realize. Jane Brody’s account of Clea’s personal experience with narcolepsy provides an excellent description of the symptoms associated with this condition “Yet during her freshman and sophomore years, she was always tired, no matter how much she slept at night. She often fell asleep in class, on the subway, while doing homework or talking to her boyfriend….. In addition to an uncontrollable tendency to nod off at inopportune times, Clea’s knees would buckle whenever she laughed or got very excited or stressed. If a minor disturbance occurred while she slept, like a paper dropping on her or her mother adjusting her covers, she woke up screaming and terrified, as if she were being attacked. And sometimes, as she was falling asleep or waking up, she would feel paralyzed, unable to move or speak.”
In more medical terms, the major symptoms of narcolepsy are :
- Excessive daytime sleepiness, with frequent daily sleep attacks or a need to take several naps during the day.
- Temporary and sudden muscle weakness, usually brought on by strong emotions.
Some, but not all, patients experience other symptoms:
- Microsleep episodes, in which the patient behaves automatically but without conscious awareness.
- A sense of paralysis that occurs between wakefulness and sleep.
- Dreamlike states between waking and sleeping.
The condition is caused by a dramatic loss of neurons producing hypocretin (also called orexin), a neuropeptide that keeps us awake. But what causes the loss of these neurons? In 2010, a team of scientists from Europe identified, in a narcoleptic patient, antibodies able to attack hypocretin neurons, indicating that the immune system could be involved in neuron loss. However, a more definitive answer comes now from a study published in Science Translational Medicine (December 18, 2013) by an international team of investigators. Results from the study show that people with narcolepsy produce T lymphocytes able to react with hypocretin and, therefore, potentially able to attack their own healthy, hypocretin-producing neurons.
These findings support the long-standing hypothesis that narcolepsy is an autoimmune disease — a disease in which people become victims of their own immune system.
There is more to this story — a link between narcolepsy and a flu vaccine. We’ll talk about it in the next post.
Copyright © 2014 Immunity Tales.
I have heard about this disease before but I had no idea that it was actually caused by an autoimmune response by our own immune system. Then the next question that came to mind was, can this disease be reversed or cured? What I found out was that, though there are treatments like antidepressants and stimulants that rectify the symptoms of narcolepsy, there isn’t anything out there that can replace hypocretin in the system. This is because hypocretin can’t be injected or given my mouth because it would break down before reaching the brain due to its molecular instability. It is possible to create drugs that can act to replace hypocretin in the brain, but the market for narcolepsy research for these types of treatments, isn’t very broad currently, so it could take a while for that to happen. Also since studies show that the hypothalamic cells that emit the hypocretin are actually terminated sometime in adolescence; so even manipulating the body to create new ones is out of the question. Therefore, finding a “cure” for this disease would have to involve creating cells that can make hypocretin and transplanting them into the brain of patients. This way, they can make new hypocretin “naturally”, consequently solving the issue at hand and not having to use medicine that isn’t attacking the origin of the problem.
Stanford School of Medicine, Center for Narcolepsy
It is indeed unexpected to read that a neurological disorder can be caused by autoimmunity. As Amina has stated, many neurological disorders are hard to treat orally because many neurotransmitters are difficult to administer to reach the brain successfully. Narcolepsy is one neurological disorder that can be treated to various degrees depending on individual cases, but can not be cured (1). A better way to treat this disorder might be to treat the immune system hypersensitivity, rather than try to replenish orexin levels in the brain.
Allergies are another type of hypersensitivity disorder that cause inflammation and other symptoms. Histamines cause dilation of blood vessels and contraction of smooth muscle, leading to hypersensitivity reactions (2). Antihistamines are drugs commonly used to to relieve allergies. This is just one example of a pharmaceutical drug that targets hypersensitivity. Obviously, the mechanism of orexin loss for narcolepsy is very different, as it involves T lymphocytes reacting with the neuropeptide. However, it may be possible to develop a drug which reduces this autoimmune activity. Making these big steps in medicine require interdisciplinary research in pharmacology, immunology, and neurobiology.
1) Medications, Stanford School of Medicine -http://psychiatry.stanford.edu/narcolepsy/medications.html
2) The Immune System, Peter Parkham, Third Edition. (G:11).
According the research article of ‘The Journal of Clinical Investigation’ about “Elevated Tribbles homolog 2–specific (Trib2) antibody levels in narcolepsy patients”, the autoimmune response was involved with the HLA-DQB1*0602 allele of the MHC molecule in humans (1). The autoimmune response also involve a T cell receptor with a particular receptor gene a variant. The article stated that the autoimmune response did not directly attack the hypocretin-producing neurons by binding to hypocretin, instead, the response is involve in the binding of the “hypocretin-coexpressed peptides”, a peptide that is destined to become a part of the hypocretin molecule, in the article’s case, the Trib2. The particular mechanism of the autoimmune response is not as obvious and it involves many mechanisms that will lead to the response. The case of losing hypocretin-producing neurons is also very specific. If we target the mechanism, where we can inhibit the binding of the coexpressed peptide to the particular MHC, we can maybe prevent the expression of antibodies. Maybe we can create a competitive inhibitor that may reduce the binding of the peptides to the MHC. The binding of the competitive substrate will inhibit the cause of an autoimmune response. Since MHC is highly polymorphic, it is hard to control the number of MHC types in the body (2). However, MHC with the particular allele can be expressed at a lower rate by inhibiting the bind of the peptide to the MHC molecule.
2. Parham, P. The Immune System. 3rd Edition
I have never heard about this disease, narcolepsy. I’ve heard of various sleeping problems, but never an autoimmune disease that causes excessive sleeping that interferes with everyday life. The only autoimmune diseases that I know are diseases like HIV/AIDS. Since I knew very little about how this disease works, I did outside research to learn more about it. There is a correlation between the H1N1 virus and narcolepsy. It is suggested that T cells that attack H1N1 can also attack hypocretin, the protein that makes you awake because “a short, 13-amino-acid section of the H1N1 hemagglutinin protein was very similar to two equally short pieces of the hypocretin protein.” Since there is a decrease in hypocretin, then the “awakeness” now goes to “sleepiness”. This could also suggest that there are other pathogens that could eventually have this ability as well. H1N1 was a mutated flu virus, and viruses mutate all the time. It’s only a matter of time before more viruses mutate, and also have the ability for the body to attack itself instead of the pathogen. I am not sure as to what we can do to have a cure for these kinds of diseases. It’s very difficult to send signals to the brain, as one of the commentors above stated, because a cure for this cannot have medicine that can be taken orally. Hopefully, more research will be conducted so we can find a cure for narcolepsy and other autoimmune diseases.
I think this article brought awareness to narcolepsy. Many don’t understand that this is a biological condition, so it can really only be treated through medicine. Because symptoms of this condition usually occurs in pre-adulthood I think it’s important for parents to constantly check for any signs of sleep disorder. Hypocretin, or orexin, is so important for neuronal function because it helps to regulate sleep and metabolism. From a study in rodents, it was concluded that food intake and metabolism is directly effected from sleep deprivation. Because humans are hormonally similar to rodents, sleep deprivation could also have a long term effect in humans. The HLA complex is associated with orexin and patients with narcolepsy display certain genetic mutations in their T cell receptors. As a result, the immune system can kill the orexin neurons. Orexin is known to influence our crave for food, so if these neurons are destroyed it can alter unhealthy future eating habits.
Sleep-Deprivation Regulates α-2 Adrenergic Responses of Rat Hypocretin/Orexin Neurons
Aaron Uschakov equal contributor,
Jeremy Grivel equal contributor, Vesna Cvetkovic-Lopes, Laurence Bayer,Laurent Bernheim, Barbara E. Jones, Michel Mühlethaler, Mauro Serafin mail
Published: February 08, 2011
I am a 63 year old female. I was diagnosed with narcolepsy at age 40 .I have cataplexey as well as other symptoms, about all of them at one time or another. I have been on different medicines over the years, some helped some didn’t. People with narcolepsy are not understood as to the debilitating effect, even by some M.D. s THAT is my problem now. So it’s very important for anyone with symptoms of narcolepsy to go to and stay with a Dr in this field not one that can change everything around to suit their needs instead of yours at any given time. I feel as if I’m having to start all over on this long road which I have battled pretty much since I’ve been a child. I simply can’t think with out the meds. NO attention span no quality of life whatsoever. I had the swine flu vaccines back in the 70 s but didn’t know there was any circumstances relating to narcolepsy until now. I also wonder about causes other than this. ..like chemical damage to a child s scalp when getting perm such as lilts and or Toni s, which were a lot stronger than perms are nowadays.