For the continuously sleepy, a new treatment shows promise

In 2005, a woman showed up at Emory University’s sleep center in Atlanta complaining of being sleepy just about every moment of every day. She slept for 14, then 16, then 18 hours a night, but still woke up feeling drowsy. Doctors had prescribed her stimulants, which worked for a bit. But when they wore off, she would go on a sleeping binge, becoming unarousable for days at a time.

Her diagnosis? Hypersomnia, a rare and debilitating condition in which people sleep excessively, are extremely drowsy while awake, and respond poorly to existing anti-sleep treatments. The condition can make people unable to work or maintain relationships.

When the woman showed up at the sleep center, researchers did a range of tests and finally took samples of her cerebrospinal fluid. They discovered it had some unusual properties. Namely, something in it caused GABA, the main neurotransmitter molecule responsible for reducing the activity of brain cells, to have an outsized effect. In essence, a mystery molecule appeared to be working with GABA to tamp down brain activity, acting as a sort of constant sleeping pill.

There’s another class of molecules that has a similar effect on GABA’s action in the brain. They are called benzodiazepines, which include Valium and Ambien.

The research team wondered whether something similar was at work in this patient, so they checked to see whether a drug used to counteract benzodiazepines, called flumazenil, would neutralize the effect of whatever was floating around in her cerebrospinal fluid. And it worked -- at least in a dish: Applying flumazenil to the woman’s cerebrospinal fluid eliminated that strange effect of GABA.

But would it work in people? That’s what the team, led by sleep expert Dr. David Rye, has been investigating since their discovery. And according to a study published Wednesday in the journal Science Translational Medicine, the answer is yes.

For the study, Rye and his team recruited seven people with various forms of hypersomnia and analyzed their cerebrospinal fluid. All had the same GABA-enhancing effect as the initial patient. And when the researchers treated the study subjects with flumazenil, they all became more alert.

According to an article on the project’s early days in Emory’s alumni magazine, that first Atlanta patient turned to her doctors after receiving the drug and exclaimed, after months of listlessness and days of nothing but sleeping, “I feel alive!” The moment brought her physicians to tears.

The finding is particularly noteworthy because flumazenil is not a stimulant and does not make normal people more alert.

Though flumazenil does appear to counteract the activity of the mysterious sleep-promoting molecule in the brains of these patients, laboratory analyses presented in the report suggest the molecule is not a benzodiazepine, and the researchers are still unsure just what it is.

That leaves the possibility that a better drug might come along for those with hypersomnia once researchers can identify what exactly causes the disorder. But for now, flumazenil appears to work well enough to get many with hypersomnia back to their lives.

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