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By Kate Kelland
LONDON, Dec 18 (Reuters) - Scientists have found that thesleep disorder narcolepsy can sometimes be triggered by ascientific phenomenon known as "molecular mimicry", offering apossible explanation for its link to a GlaxoSmithKline H1N1 pandemic flu vaccine.
Results from U.S. researchers showed the debilitatingdisorder, characterised by sudden sleepiness and muscleweakness, can be set off by an immune response to a portion of aprotein from the H1N1 virus that is very similar to a region ofa protein called hypocretin, which is key to narcolepsy.
This can happen in genetically susceptible people, theresearchers said, adding that around 20 percent of the Europeanpopulation have the genetic profile making them vulnerable.
Previous studies in countries where GSK's Pandemrix vaccinewas used in the 2009/2010 flu pandemic have found its use waslinked to a significant rise in cases of narcolepsy in children.
Studies in Britain, Finland, Sweden and Ireland found such alink, and GSK says at least 900 narcolepsy cases associated withthe vaccine have so far been reported in Europe.
Narcolepsy is thought to be brought about by loss offunction in "wakefulness" cells called hypocretin cells in oneof the brain's sleep centres.
CROSS-REACTIVITY
Emmanuel Mignot, a narcolepsy researcher and director of theStanford Center for Sleep Sciences and Medicine who has beenfunded by GSK to look deeper into the link, said therelationship between H1N1 infection, vaccination and narcolepsygave his team "some very interesting insight into possiblecauses of the condition".
In particular, he said, it strongly suggested that thedefences, or T cells, of the immune system primed to attack H1N1can occasionally also cross-react with hypocretin and somehowcause the destruction of brain cells that produce hypocretin.
"When we saw that the portion of the hypocretin that seemedto be recognised by the immune system in narcolepsy patients wassimilar to a part of the pandemic 2009 H1N1 influenzahemagglutinin molecule, we were very hopeful that we were on theright track," said Mignot's co-researcher Elizabeth Mellins,also at the Stanford University School of Medicine.
The Pandemrix vaccine mixed portions of viral proteins witha non-viral "adjuvant", or booster, designed to induce astronger immune response. The shot was never used in the UnitedStates and has been withdrawn from use in Europe since the linksto narcolepsy emerged.
The researchers said their study provided compellingevidence of "molecular mimicry" - the idea that because of asimilarity between a pathogen protein and a human protein, thenormal immune response to a pathogen, such as H1N1 flu, could insome people go awry, triggering the immune system to mistakenlyattack healthy components of the body.
Mignot said the findings, published in the journal ScienceTranslational Medicine, could pave the way to a new blood testto diagnose narcolepsy.
They also point towards potential new ways to try tointervene in narcolepsy before the specialised brain cells havebeen destroyed and led to the worst level of symptoms.
"This study will shape the next decade of research intonarcolepsy," Mellins said.
Mignot, Mellins and their team now plan to study how T cellcross-reactivity to hypocretin can destroy the hypocretin cellsin the brain, and whether this process could potentially beblocked to potentially prevent narcolepsy.
