Grant: Project Grant

Sleep apnea is a serious respiratory disease affecting millions of Canadians. Medical devices for the treatment of sleep apnea continue to improve. However, the ability to comply with device-based treatments over long periods remains mixed. Sensory organs in the neck, the carotid bodies, are likely critical to the pathology of sleep apnea. When breathing is insufficient to supply enough oxygen to the body, these organs tell the brain to increase breathing and deliver more blood to tissues; when the reverse is true, they tell the brain to reduce or stop breathing. Usually, oxygen and carbon dioxide are tightly regulated, but in sleep apnea the carotid bodies become sensitized. This leads to exaggerated breathing responses to changes in oxygenation, destabilizing breathing and causing high blood pressure. Important questions regarding the treatment of sleep apnea patients are thus, why are the carotid bodies sensitized, and how can this be reversed? This proposal addresses both questions with the aim to identify novel and/or repurpose existing drugs to treat sleep apnea. Our preliminary data identify novel mechanisms of carotid body sensitization caused by fluctuating oxygenation and signalling molecules resulting from inflammation, both associated with respiratory disease. In addition, our data suggest that the effects of these mechanisms on carotid body activity can be reversed by somatostatin. This is significant because somatostatin analogues are already approved for treatment of acromegaly, circumventing the most expensive and time-consuming drug development stages. We propose to confirm the above data, investigate receptors involved, and test if somatostatin analogues can be used to treat sleep apnea. This project will help us understand carotid body function and its involvement in respiratory disease. Importantly, this project will also test feasibility of repurposing clinically-approved somatostatin analogues while identifying new targets for drug discovery.