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A Sleep Gene Has A Surprising Role In Migraines

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Mutations on a single gene appear to increase the risk for both an unusual sleep disorder and migraines, a team reports in Science Translational Medicine.

The finding could help explain the links between sleep problems and migraines. It also should make it easier to find new drugs to treat migraines, researchers say.

And for one member of the research team, Emily Bates, the discovery represents a personal victory.

Bates remembers getting a lot of migraines in elementary school. They would start with nausea and changes in vision, she says. Then came the pain.

"Loud sounds and light kind of hurt my eyes and my ears and my head," she says. Moving or applying any sort of pressure to her skin also hurt.

The problem was embarrassing and caused her to miss a lot of school, Bates says. It also was frustrating, she says, because back then, in the 1990s, no one could tell her much about what was causing her migraines or how to stop them.

So Bates decided to become a scientist in order to understand "these bizarre, awful migraines." She earned a doctorate in genetics at Harvard in 2005. Then, a couple of years later, while working in a lab at the University of California, San Francisco, she got a remarkable opportunity.

Researchers in Los Angeles had been studying a family with a lot of migraines. The team discovered something really surprising about this family: They were early birds who were usually asleep by 8 p.m. and up by 5 a.m. The scientific name for the condition is "advanced sleep phase."

The researchers were able to trace the family's sleep disorder to a mutation on a gene that helps control circadian rhythms, says Andrew Charles, a neurologist at UCLA. "We then turned our attention to the question of how this gene mutation could be involved in migraine," he says.

The first step was to show that the gene really could cause both sleep problems and migraines. So the team found a second family being studied at UCSF that had a slightly different mutation on the same gene. Sure enough, many members of this family were also early birds who had migraines.

The next step was to study mice carrying the mutated gene. And that's where Emily Bates got a chance to help explain the disorder that had so disrupted her childhood.

Bates' boss at UCSF, Louis Ptacek, had asked her to study the behavior of mice carrying the mutated gene and to find out whether they were experiencing any symptoms of migraines.

There's no sure way to know if a mouse has a headache, Bates says. So she began looking for some of the other migraine symptoms she knew so well — things like sensitivity to heat and touch — and she found them.

"All of the things that we looked at basically said these mice are more susceptible to migraine than a normal mouse," she says. The mice also had brain changes similar to those seen in people experiencing a migraine.

The findings should help explain the elusive link between sleep patterns and migraine, Charles says. "Disruptions of sleep are very well known to be a migraine trigger," he says. "And many migraine patients will tell you that their migraine attack will only end if they're able to get to sleep."

The results also serve as a reminder that there is a lot more to a migraine than headache and pain, Charles says. He says the study represents "another step toward bringing migraine forward as a disorder of the brain and a disorder for which there's a genetic basis."

But the ultimate payoff of the new research should be new ways to treat or prevent migraines, says Bates, who is now on the faculty at Brigham Young University.

"I know so well how frustrating and really demoralizing it can be to get a migraine," she says. "But I think once we understand the mechanism we can design better drugs."

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