The disease is due to loss or impairment of the orexin/hypocretin neurons of the lateral hypothalamus that results in decreased hypocretin-1 levels in the cerebrospinal fluid. Other, non specific, clinical signs include hypnagogic hallucinations, sleep paralysis, disturbed nocturnal sleep, and weight gain, especially in children. The average time between the age of appearance of the symptoms and the diagnosis is still very long, 10 years. The age of onset varies between 10 and 30 years old and symptoms are lifelong. And there aren’t any drugs that can replace it.Narcolepsy type 1 prevalence is estimated between 1/2,000 and 1/5,000. Part of the issue is that once you lose hypocretin, it’s gone. But Mohsenin says those experiments haven’t worked yet. Researchers have also tried to figure out if drugs that target the immune system - immunomodulators - can treat narcolepsy. And Kornum says there’s “quite a lot of effort going into understanding the T cell picture better.” One way to do that, she says, could be through better animal and mouse models that copy the human autoimmune process. There’s more to learn about which gene changes are most important for raising your odds of narcolepsy. That’s why you can see elements in healthy people, but they didn’t have everything at the same time.” Where Is Research Headed? “The thinking, right now, is that to develop the disease, you need a combination of everything. She says that includes your genes, T cells, and outside triggers - such as a viral infection like the flu. Kornum agrees that narcolepsy is probably a mix of “unfortunate” factors. “That’s another indirect piece of evidence indicating immunity in narcolepsy,” Mohsenin says. And studies show that people who have the HLA gene for narcolepsy have a higher antibody response to that protein. Some experts think that a protein from that flu shot, or the infection itself, reacted with hypocretin-producing cells. Those areas saw a spike in narcolepsy cases compared to prior years. He says certain countries used a flu vaccine that we didn’t use in the United States. Mohsenin points to events from the 2009 H1N1 flu epidemic. Like other health conditions, it’s likely your genes and environment affect each other. That makes the genetic part of narcolepsy “interesting and confusing,” Mohsenin says. And some people without narcolepsy have a mutated HLA gene. But you can still have narcolepsy with a normal HLA gene. People with narcolepsy type 1 are much more likely to have mutations, or changes, in a group of genes called human leukocyte antigen (HLA). Kornum says researchers are comparing the two conditions because of their similarities. Other autoimmune conditions, such as type 1 diabetes, also have autoreactive CD8+ T cells. “But it all points in the same direction: There’s something with the immune system that’s specifically targeting these neurons, and they’re lost,” Kornum says. This doesn’t prove that these T cells are the ones destroying hypocretin. That means these T cells can detect and target cells that make hypocretin. Studies, including Kornum’s research, have found that people with narcolepsy have CD4+ and CD8+ T cells that are autoreactive toward hypocretin neurons. These cells can do damage alone or by helping other immune cells. CD4+ and CD8+ T cells are building blocks for autoimmunity, says Insoo Kang, MD, a rheumatologist with Yale Medicine in Connecticut. That’s called autoimmunity.Ĭertain types of immune cells called T cells are involved in this process. So, it attacks them and other healthy tissue. But sometimes it thinks your own cells might hurt you or make you sick. Your immune system protects you from germs, including viruses and bacteria. “But nothing has panned out to be specific enough to explain any type of narcolepsy - whether it’s type 1, type 2, or something in between.” “There’s been a lot of time and money spent to identify an autoimmune antibody,” says Vahid Mohsenin, MD, a sleep medicine specialist with Yale Medicine and professor of medicine at Yale School of Medicine in Connecticut. Most research is done on type 1 because it’s far more common and there’s hypocretin loss. She hasn’t found a specific narcolepsy-related antibody, but “the autoimmune hypothesis is the best explanation that captures all the findings we have so far.” Now there’s growing evidence an autoimmune process might trigger this loss.īirgitte Kornum, PhD, an associate professor in the department of neuroscience at the University of Copenhagen, studies sleep and the immune system. Also called hypocretin, that’s a brain chemical that controls wakefulness. But most people with type 1 narcolepsy - the kind with sudden muscle weakness, or cataplexy - have little to no orexin. We still don’t know what causes the condition. Narcolepsy is a neurological disorder that affects your sleep-wake cycle.
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