0067 Humanized Chemogenetic Approach to Treat Sleep Apnea

[摘要] IntroductionObstructive Sleep Apnea (OSA) is a prevalent condition and a major cause of morbidity and mortality. OSA contributes to the development and progression of neurocognitive, metabolic, cardiovascular, and oncologic diseases. The tongue and specifically genioglossus (GG) muscle have been implicated in the pathogenesis of upper airway (UA) obstruction during sleep. Nasal positive airway pressure can treat OSA but poor adherence severely limits its effectiveness. We have previously shown that obese C57BL/6J mice have OSA, similar to humans. We have also shown that DREADDs deployed by intracerebral injection in the XII nucleus and activated with specific ligand clozapine-N-oxide (CNO) increases UA patency in mice. Several challenges preclude the translational use of our previous approach including (a) intracerebral injections; (b) CNO conversion psychotropic active clozapine. We hypothesized that, in mice, UA patency can be improved and sleep apnea can be treated by injecting DREADD carried by an adeno-associated virus type 9 (AAV9) capable of retrograde neuronal transport and activated by a novel ligand JHU37160 (J60).

[学科分类] 生理学