1. Sep, 2013

Emory University's “mystery somnogen”

Emory University’s discovery of a “mystery somnogen” that they believe causes a sub group of IH sufferers to feel like they are being constantly sedated and the drugs they have found reverse this affect.

In 2007 Kathy Parker, then an Emory University School of Nursing faculty member and one of only a handful of nurses in the United States board-certified in sleep medicine and Andrew Jenkins, an Emory molecular pharmacologist, anesthesiologist and GABA expert along with Dr David Rye a clinician scientist and professor in neurology at Emory set about finding out what caused the disabling hypersomnolence in one of their patients, Anna Sumner. In May 2007, they gave her a spinal tap, an invasive procedure that collects cerebrospinal fluid (CSF), the clear substance that’s produced in the middle of the brain and flows down the spinal cord. They found it contained a high level of a substance that, like benzodiazepines (the active ingredients in drugs such as Valium & Xanax) activates the chemical messenger GABA. This neurotransmitter acts as a shutdown switch in the brain, dialing down consciousness so we can sleep. 

The results of their tests suggested Anna’s brain was putting itself to sleep by producing its own private reserve of chemical anesthetic, which amplified GABA’s effects (ie: rather than producing too much GABA the problem was that Anna was hypersensitive to it). The outcome was comparable to sedating doses of Versed, a benzodiazepine drug commonly used during extraction of a wisdom tooth or a colonoscopy. Dr Jenkins joked with Anna that if another woman were carrying around the same amount of GABA-activating sedative, she could practically be operated on.

The problem was that the current medications such as stimulants and wake promoting drugs were not effective. Dr Jenkins described it as like flooring the gas pedal in a car with the park brake engaged. Such a strategy might bring physical alertness — as evidenced by typical symptoms like twitchiness and high blood pressure caused by these medications — but a disabling mental dullness lingered. Eventually the medications became completely ineffective and Anna was back to sleeping ridiculously long hours.

Recent research by Emory has found in a test tube model of the disease, that the drugs flumazenil and Clarithromycin do in fact return the function of the GABA system to normal. Flumazenil is usually used in cases of overdose of benzodiazepines, a widely used class of anesthetics and sedatives such as diazepam (Valium) and zolpidem (Ambien). It is also used to reverse the effects anesthesia. Clarithromycin is an ordinary antibiotic. They have not explained why this particular antibiotic has been found to reverse the effects of the sedation found in some patients with IH however it is important to note that the positive effect of clarithromycin is secondary to a benzodiazepine antagonist-like effect, not its antibiotic effects, and treatment must be maintained. 

Dr. David Rye, Connectome interview: Deciphering Sleep

"The real question now is, is this biological agent unique to the types of hypersomnia we studied, or might it also be a factor in other known types of narcolepsy that we didn’t look at? Or might it be part of a general-purpose pathway to sleepiness, common to all human brains?"