Upregulation of GABA Signaling for the Treatment of Acquired Cognitive Deficits

Background & Unmet Need

• Loss of organized sleep electrophysiology is a characteristic finding after severe brain injury
• Acquired cognitive deficits may lead to loss of autonomy and independence and significantly impact patient quality of life
• Recent studies have implicated daytime brain activation as a modulator of sleep architecture in the severely injured brain
• Unmet Need: Novel therapeutics for patients who experience continued cognitive deficits following brain injury

Technology Overview

• The Technology: Treatment of acquired cognitive deficits through upregulation of GABAB signaling
• The Discovery: Administration of sodium oxybate (SO) in mice right before sleep generated an increase in the delta oscillations (1-4Hz) LFP power in the non-REM
• Administration of SO at night increased beta (20-40Hz) and gamma (>40Hz) LFP during the subsequent wakeful period
• An increase in beta and gamma frequency power is associated with the recovery of complex behaviors in a wakeful state

Technology Applications

• Treatment of cognitive deficits following brain injury, or in association with chronic disease or psychiatric disturbance
• Improvement of wakeful function

Technology Advantages

• Upregulation of GABAB signaling at night may be coupled with anterior-forebrain stimulating therapy when the subject is awake
• Several upregulators of GABA signaling are already approved for other indications (e.g., baclofen, tiagabine, zolpidem, midazolam)