The ‘Need to Knows’ of Narcolepsy
With close to 3 million hits, the narcoleptic poodle named Skeeter has become somewhat of a youtube sensation. But what is known about narcolepsy in humans and can anything be done to treat it?
What is narcolepsy?
Narcolepsy is a rare disorder which affects around 20 in every 100,000 people worldwide and is characterised by a number of very visible and debilitating symptoms (Mayer, 2013). The first, known as excessive daytime sleepiness, sees the individual falling asleep at inopportune times and places. The second is termed cataplexy and involves a sudden loss of muscle control, often in response to an emotional trigger. About 20–50% of people with narcolepsy have this symptom (Mignot, 2011). Other symptoms include night-time insomnia, dream-like hallucinations and sleep paralysis as the individual is going to sleep or waking up.
What causes narcolepsy?
There are a number of hypotheses as to what causes narcolepsy. The strongest and most documented of these relates to an important substance called hypocretin (or orexin), produced by certain neurons in the brain. Hypocretin is known to be involved in regulating sleep/wakefulness states and feeding behaviour but is depleted in people with narcolepsy and cataplexy (though not always in those without cataplexy). Individuals with narcolepsy and cataplexy also show a 90% or more reduction in the number of hypocretin-producing neurons in their brains (Mahlios et al, 2013). In dogs like Skeeter and mouse models of narcolepsy, the condition has been traced back to abnormalities in the genes coding for hypocretin (Sakurai, 2013). Importantly, these findings have led scientists to believe that this loss of hypocretin may underlie narcolepsy (with cataplexy).
Though widely debated, a number of studies have suggested that an autoimmune response may be to blame for the reduced number of hypocretin-producing cells and, consequently, narcolepsy. Put briefly, when a foreign substance such as a virus or bacteria (termed a pathogen) invades a person’s body, their immune system produces special proteins (known as antibodies) to destroy that pathogen. In an autoimmune condition, however, a person’s immune system mistakenly attacks the healthy cells in their body. Recently, a family of proteins found in abundance in hypocretin neurons has been linked to the destruction of these neurons. Since people with narcolepsy seem to have much higher levels of antibodies against this family of proteins, it is possible that these proteins could play a role in the narcolepsy disease process (Mahlios et al, 2013).
How is narcolepsy treated?
Therapy for narcolepsy currently focuses on treating the symptoms of the disease: mainly the excessive daytime sleepiness and the cataplexy. The first is treated with stimulants such as amphetamines, caffeine and a drug called modafinil. These act to increase the substances in the brain responsible for promoting wakefulness and have been effective in many patients. These medications may have side effects, however, including tremor, irritability and the potential for addiction. The only approved treatment of cataplexy (in those patients who have it) is a drug called sodium oxybate. Contrary to the stimulants above, sodium oxybate works to slow down brain activity and has been shown to significantly reduce cataplexy in clinical trials, though the side effects include dizziness, confusion and in more serious cases, comas (Mayer, 2013).
What is next?
Clearly, further research is needed to understand the disease process involved in narcolepsy and thus develop more effective treatments for individuals living with this condition. Such therapies may even help Skeeter stay awake long enough to enjoy dinner.
Mayer G, Bassetti C, Dauvilliers Y. 2013. Treatment options in narcolepsy. Expert Opinion. 1: 987–99. http://informahealthcare.com/doi/abs/10.1517/21678707.2013.854701.
Mahlios J, De la Herrán-Arita A, Mignot E. 2013. The autoimmune basis of narcolepsy. Current Opinion in Neurobiology. 23: 767–73. http://www.ncbi.nlm.nih.gov/pubmed/23725858.
Mignot E. 2011. Etiology and genetics of human narcolepsy. In Baumann CR, Bassetti C, Scammell T (eds.) Narcolepsy: pathophysiology, diagnosis and treatment. NY: Springer: 3–17. http://link.springer.com/chapter/10.1007%2F978-1-4419-8390-9_1.
Sakurai T. 2013. Orexin deficiency and narcolepsy. Current Opinion in Neurobiology. 23: 760–6. http://www.ncbi.nlm.nih.gov/pubmed/23663890.