Narcolepsy May Be an Autoimmune Disease

This article was originally posted on RealClearScience.

Fans of the 2001 movie Rat Race will remember that Rowan Atkinson’s character suffered from narcolepsy. Moments before claiming the $2-million cash prize, he fell asleep. In real life, not only do narcoleptics suffer from irresistible daytime sleepiness, but they also have trouble sleeping at nighttime and may physically collapse from sudden muscle weakness, a symptom known as cataplexy. But, what causes it?

Evidence over the past few years has suggested that narcolepsy is an autoimmune disorder. However, the evidence is rather scattered; some data implicates environmental triggers, while others suggest genetic factors. Last December, a report linking an influenza vaccine with narcolepsy supposedly provided confirmation of the underlying autoimmune nature of the disease, but the article was later retracted due to a failure to replicate key findings. Still, the suspicion about narcolepsy remained.

Now, a new study in PNAS provides very strong evidence that some cases of narcolepsy are indeed due to autoimmunity. The authors report that human antibodies (immune proteins that attack foreign substances) from narcoleptics bind to molecules in rat brains, specifically neuropeptides, which are signaling molecules. (See chart. Note: OSRD = other sleep-related disorders; HCs = healthy controls; MC = military controls; A, B, and C refer to different patterns of antibody binding in the brain.)

As shown, 27% of narcoleptics and 22.5% of people with other sleep-related disorders had antibodies which could bind to various molecules within the rat brain, compared to just 10.4% of healty controls and 10% of military recruits. This means that narcoleptics (and those with other sleep disorders) are twice as likely to have autoreactive antibodies as healthy people.

The authors then injected antibodies from two narcoleptics and a healthy control into rats. The narcoleptics’ antibodies altered the rats’ sleeping patterns, for instance, by causing them to exhibit fragmented sleep. However, the rats did not fall asleep uncontrollably (the main symptom of narcolepsy), perhaps because the researchers only injected them once with the antibodies, rather than multiple times (which would mimic a chronic condition).

The data provides very strong evidence that a proportion of narcoleptic patients, as well as those who suffer other sleep disorders, are suffering from an underlying autoimmune condition. However, the data also suggests that this applies to only 1/4 of all narcoleptics, meaning that, most likely, there are multiple causes for this mysterious disorder.

Source: Peter Bergman et al. “Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns.” PNAS. Published online before print: 18-Aug-2014. doi: 10.1073/pnas.1412189111