Finding the Narcolepsy Target

A new study provides evidence to support the idea that narcolepsy is an autoimmune disorder.

A decade ago it was discovered that people with narcolepsy lack brain cells that make “hypocretin.” This is a hormone that helps promote wakefulness. The finding helped explain why people with narcolepsy have episodes of uncontrollable sleepiness.

But why do these brain cells die in people with narcolepsy? Last year the Sleep Education Blog reported on a new study. It suggested that the immune system attacks and destroys the brain cells by mistake. In August another study reported that this attack may be triggered by an infection.

Now Swiss and French researchers report that they may have identified a specific target of the autoimmune attack that causes narcolepsy. It is a protein called Tribbles homolog 2 – or “Trib2.”

They believe that Trib2 is an “autoantigen” in narcolepsy. An autoantigen is the target of an attack by autoantibodies. These antibodies attack a natural protein in the body rather than a protein from an infectious agent.

First they found that Trib2 was enriched in hypocretin-producing neurons in mice. Then they compared people who have narcolepsy with healthy controls. They also compared narcoleptics with people who have other disorders such as idiopathic hypersomnia and multiple sclerosis.

They found that the levels of Trib2-specific antibodies were much higher in people with narcolepsy. These levels of circulating autoantibodies against Trib2 were highest soon after narcolepsy symptoms appeared. They sharply decreased within two to three years.

Then the levels of Trib2-specific antibodies stabilized for up to 30 years. But these levels remained much higher than those of controls.

“These results indicate for the first time to our knowledge that Trib2 is an autoantigen in human narcolepsy,” the authors wrote. “Trib2-specific antibodies specifically target hypocretin neurons, ultimately leading to their disappearance and hypocretin deficiency.”

They cautioned that Trib2 may not be the only autoantigen in narcolepsy. Several autoantibodies may be involved.

But they are optimistic about treating narcolepsy with intravenous immunoglobulins soon after symptoms appear. In 2003 and 2004 they reported success at using IVIg treatment for people with narcolepsy. Last year they reported that hypocretin levels normalized in a narcolepsy patient after immunotherapy.

Read more about narcolepsy.

Image by Op.dan