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New Research Offers Insights into the Cause of Narcolepsy

An international team of researchers led by Lawrence Steinman, MD, of Stanford University, has found some of the first solid evidence that narcolepsy may be a so-called “hit-and-run” autoimmune disease. Results of the study were published July 1 in the journal Science Translational Medicine.

Autoimmune diseases such as multiple sclerosis and rheumatoid arthritis are known for taking decades to damage the body’s systems. But since the late 1990s, researchers have suspected that there is another kind of autoimmune disease, one that causes rapid, pinpoint damage. Researchers suspect that narcolepsy is one of these “hit-and-run” diseases.

Narcolepsy occurs mostly at random, as opposed to being inherited, although a gene variant called HLA-DQB1*0602 can make people more susceptible to it. The gene variant itself does not cause narcolepsy. Instead a combination of the genetic predisposition and infection triggers narcolepsy in some people.

In this study, the researchers looked at why only one of the vaccines used during the 2009 swine flu pandemic was associated with a spike in narcolepsy cases. After the 2009 pandemic, researchers saw an increase in the number of new narcolepsy cases, but only in some places. People who had been immunized with GlaxoSmithKline’s Pandemrix vaccine, which was used only in Europe, showed an increase in narcolepsy, but those immunized with Novartis’ Focetria did not.

The researchers team found that the H1N1 virus contains a protein whose structure is similar to a portion of a human hypocretin receptor, and that the Pandemrix vaccine contained a much higher amount of this protein than the Focetria vaccine.

The authors propose a hit-and-run autoimmune mechanism for how both swine flu and Pandemrix might cause narcolepsy. They suggest that in genetically predisposed people, high levels of the H1N1 protein, introduced either by the virus itself of the Pandemrix vaccine, stimulate the production of a large number of antibodies that attack the flu virus, as well as the hypocretin receptors which are similar in structure. This leads to the destruction of brain cells that are critical to regulating sleep-wake cycles and causes narcolepsy in these individuals.

While this research advances the understanding of narcolepsy, it does not definitively explain narcolepsy’s cause. Experts say much more research is still needed.

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Date Created: July 13th, 2015
Last Updated: April 7th, 2017