O002 A novel, optogenetics based therapy for obstructive sleep apnea

INTRODUCTION: Many obstructive sleep apnea (OSA) patients are sub-optimally treated due to poor tolerance or incomplete response to established therapies. We propose a novel stimulation therapy that sensitises the dilator muscles to light activation (‘optogenetics') and activates the muscles with light during sleep. This study aims to determine feasibility in a rodent model of OSA and identify effective optogenetic constructs. METHODS: Rats received intramuscular injections of a viral vector encapsulating the opsin ChR2, driven by either a muscle-specific or non-specific promotor. Three weeks post-injection, opsin expression was quantified via confocal imaging. Light-induced tongue muscle activity afforded by the superior promotor was then measured in an acute model of OSA. The superior promotor was then combined with a novel muscle-targeted viral vector and, light-induced airway dilation was measured with ultrasound imaging. RESULTS: With the muscle-specific promotor, opsin expression in the tongue was 470%(p=0.013, RM-ANOVA) greater, and brainstem expression was abolished. In the animals who received this superior promotor, light stimulation facilitated a 56% increase in muscle activity from that recorded during unstimulated breaths in an acute model of OSA(p<0.001, linear mixed model). Ultrasound imaging confirmed that light stimulation of the optogenetic construct with a muscle-specific promotor encapsulated in a muscle-targeted viral vector produced airway dilation in the same OSA model. DISCUSSION: The combined muscle-specific promotor and muscle-specific viral vector resulted in a novel and highly effective method of inducing light-sensitivity in upper airway muscles and facilitating light-induced airway dilation. This study provides proof-of-concept for a non-invasive optogenetics-based OSA therapy.