Grant: Proof of Principle Program - Phase II

DEVELOPMENT OF A NOVEL DRUG THERAPY THAT STIMULATES THE BRAIN TO INCREASE WEAK BREATHING IN BABIES AND ADULTS There are a number of clinical situations that result in weak breathing movements or the temporary stoppage of breathing (called apneas). Repeated bouts of weak breathing or apnea lead to poor oxygen delivery to our organs and tissues that can impair their function. Further, there is a powerful stress response to the repeated bouts of near suffocation that lead to impaired memory and mental ability and increased risk of stroke, diabetes and cardiovascular disease. My laboratory has demonstrated that a novel class of drug, called ampakines, is very effective in countering drug-induced respiratory depression, including in an early stage clinical trial. We will extend those studies with ampakines toward understanding how they actually alter brain cells to stimulate breathing and determine if this therapy has promise for treating weak breathing after exposure to opioid pain-killers/anesthetics, in prematurely born babies, patients with spinal cord injury, Pompe Disease, exposed to West Nile Virus or neurodegenerative diseases. This will be essential for achieving the ultimate goal of having ampakines being used routinely world-wide for a variety of unmet clinical needs.