Emory Team to Receive Grant to More Fully Understand and Release the Parking Brake!
The Hypersomnia Foundation congratulates Dr. David Rye and the team at Emory University on their receipt of a 4-year award for nearly $3 million in total costs from the National Institute of Neurological Disorders and Stroke to study the biologic basis of hypersomnia. This funding will enable the team to further characterize “an endogenous GABA-ergic mechanism underlying hypersomnia.” According to Dr. Rye’s grant application: “Sleepiness that persists after prolonged sleep (i.e., hypersomnia) is common, its socioeconomic burden significant, and its origins poorly understood. Recognition and treatment are inadequate. We have shown that the spinal fluid of patients disabled by sleepiness mimics sedative-hypnotic drug actions. Reversal with benzodiazepine antagonist drugs in vitro restores wakefulness to patients failing standard therapies. We propose to identify the molecule that is causal to this sleepiness and define its subcellular site of action relative to that targeted by conventional sedative/hypnotic drugs.”
As reported in their seminal 2012 Science Translational Medicine paper, Emory researchers have identified an “endogenous small peptide that dampens neural excitability by enhancing gamma-aminobutyric acid (GABA)—the brain’s principal inhibitory neurotransmitter. The [cerebrospinal fluid] of patients [with primary hypersomnias] exhibit normal GABA concentrations and amino acid profiles, and do not contain exogenous benzodiazepines by forensic liquid chromatography/mass spectrometry.”
This research has the potential to turn on its head our current understanding of how sleepiness occurs.
As Dr. Rye is oft to paraphrase collaborator Dr. Andrew Jenkins, “The current treatment modalities for hypersomnia (that is, with psychostimulants or alternate agents that promote wake) are analogous to pushing the gas pedal of a car while the parking brake is engaged. . . no matter how much the drivers accelerate, they cannot fully overcome the parking brake. We need to better understand the parking brake—and how to release it—to bring more complete relief from hypersomnia.” In the words of the grant application, “The idea that hypersomnolence can arise from a gain of function of a naturally occurring humoral somnogen is a paradigm shift from concepts that posit a cause in loss of function of wake-promoting neural networks.”