Narcolepsy: Trouble With Tribbles?

A major cause of narcolepsy appears to be trouble with
tribbles.

The tribbles in question are bits of RNA amusingly named after the cute
and furry but dangerously fertile creatures made famous in a Star Trek
TV episode. Not at all amusing is what happens when the body makes antibodies
that attack tribbles in sleep -regulating brain cells.

New findings strongly suggest that anti-tribbles antibodies kill a
population of brain cells that regulates sleep. This triggers narcolepsy,
particularly the severe manifestation of narcolepsy called cataplexy, in which
strong emotions trigger paralysis.

"We have identified reactive autoantibodies in human narcolepsy, providing
evidence that narcolepsy is an autoimmune disorder," conclude Vesna
Cvetkovic-Lopes and colleagues of the University of Geneva, Switzerland.

Scientists have long suspected that anti-self immune responses --
autoimmunity -- play a role in narcolepsy. People with narcolepsy have a
dramatic loss of brain cells that produce hypocretin (also known as orexin ), a
chemical messenger crucial to normal sleep patterns.

But until now, nobody has been able to find abnormal immune responses in
people with narcolepsy.

Using mice genetically engineered
to overproduce tribbles, Cvetkovic-Lopes and colleagues screened for hypocretin
structures that might be targets for immune attack. They found that
hypocretin-producing brain cells make a large amount of a specific type of
tribbles -- tribbles homolog 2 or Trib2.

Then they looked for the
antibodies in people who had narcolepsy and people who didn't. Sure enough, the
researchers found narcolepsy patients -- but not other people -- have a lot of
antibodies against Trib2.

"These results indicate for the first time to our knowledge that Trib2 is an
autoantigen in human narcolepsy and that Trib2-specific antibodies specifically
target hypocretin neurons, ultimately leading to their disappearance and
hypocretin deficiency," Cvetkovic-Lopes and colleagues conclude.

The finding does not prove that autoimmunity is behind all forms of
narcolepsy. But some patients may benefit from the findings.

The researchers have already treated patients recently diagnosed with
narcolepsy with immune globulins. These experiments, they report, had
"unexpected positive results, suggesting that the autoimmune process may be
counteracted if treated early."

The findings appear in the Feb. 15 online issue of the Journal of
Clinical Investigation.

By Daniel DeNoon
Reviewed by Louise Chang
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