Designer Receptors Exclusively Activated by Designer Drugs Approach to Treatment of Sleep-disordered Breathing.

American Journal of Respiratory and Critical Care Medicine
Thomaz A Fleury CuradoVsevolod Y Polotsky

Abstract

Rationale: Obstructive sleep apnea is recurrent upper airway obstruction caused by a loss of upper airway muscle tone during sleep. The main goal of our study was to determine if designer receptors exclusively activated by designer drugs (DREADD) could be used to activate the genioglossus muscle as a potential novel treatment strategy for sleep apnea. We have previously shown that the prototypical DREADD ligand clozapine-N-oxide increased pharyngeal diameter in mice expressing DREADD in the hypoglossal nucleus. However, the need for direct brainstem viral injections and clozapine-N-oxide toxicity diminished translational potential of this approach, and breathing during sleep was not examined.Objectives: Here, we took advantage of our model of sleep-disordered breathing in diet-induced obese mice, retrograde properties of the adeno-associated virus serotype 9 (AAV9) viral vector, and the novel DREADD ligand J60.Methods: We administered AAV9-hSyn-hM3(Gq)-mCherry or control AAV9 into the genioglossus muscle of diet-induced obese mice and examined the effect of J60 on genioglossus activity, pharyngeal patency, and breathing during sleep.Measurements and Main Results: Compared with control, J60 increased genioglossus tonic activity ...Continue Reading

References

Jul 3, 1995·The Journal of Comparative Neurology·E G Dobbins, J L Feldman
Aug 1, 1994·Journal of Applied Physiology·C L MarcusA R Schwartz
Apr 1, 1993·The American Review of Respiratory Disease·N B KribbsD F Dinges
Jul 4, 2001·American Journal of Respiratory and Critical Care Medicine·C L Marcus
Jan 10, 2002·American Journal of Respiratory and Critical Care Medicine·Atul MalhotraDavid P White
Feb 22, 2007·Sleep·David W CarleyMiodrag Radulovacki
Jan 21, 2010·Physiological Reviews·Jerome A DempseyChristopher P O'Donnell
Apr 7, 2010·Sleep Medicine·Sergio TufikLia Rita Azeredo Bittencourt
Jul 2, 2011·Journal of Applied Physiology·Mikhael PolotskyAlan R Schwartz
Feb 22, 2012·Journal of Applied Physiology·Mikhael PolotskyAlan R Schwartz
Sep 4, 2012·Neuromodulation : Journal of the International Neuromodulation Society·Faisal N ZaidiTerence M Davidson
Dec 12, 2012·American Journal of Respiratory and Critical Care Medicine·Kevin P GraceRichard L Horner
Apr 17, 2013·American Journal of Epidemiology·Paul E PeppardKhin Mae Hla
Jul 3, 2013·Journal of Applied Physiology·Alan R SchwartzArie Oliven
Dec 18, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mai K ElmallahDavid D Fuller
Jan 10, 2014·The New England Journal of Medicine·Patrick J StrolloUNKNOWN STAR Trial Group
Apr 3, 2014·The Journal of Physiology·Zoltan A TorontaliJohn H Peever
Dec 19, 2014·The International Journal of Neuropsychopharmacology·Hu Zhu, Bryan L Roth
Feb 16, 2015·The Lancet. Respiratory Medicine·R HeinzerJ Haba-Rubio
Mar 31, 2015·Journal of Applied Physiology·Yaniv DotanArie Oliven
Feb 20, 2016·Neuron·Bryan L Roth
Mar 12, 2016·American Journal of Respiratory and Critical Care Medicine·Luigi Taranto-MontemurroAndrew Wellman
May 20, 2016·Genesis : the Journal of Genetics and Development·Hu ZhuUte Hochgeschwender
May 29, 2016·Sleep Medicine Clinics·David P White
Sep 30, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Isabel F AugurJamie Peters
Mar 11, 2017·Scientific Reports·Thomaz Fleury CuradoVsevolod Y Polotsky
Apr 7, 2017·Scientific Reports·Garret A HortonRichard L Horner
Jul 3, 2017·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Michael F NasoWilliam R Strohl
Aug 5, 2017·Science·Juan L GomezMichael Michaelides
Sep 18, 2018·Chest·Thomaz Fleury CuradoAlan R Schwartz
Nov 6, 2018·American Journal of Respiratory and Critical Care Medicine·Luigi Taranto-MontemurroAndrew Wellman
Nov 30, 2018·Frontiers in Neurology·Thomaz A Fleury CuradoVsevolod Y Polotsky
Dec 7, 2018·American Journal of Respiratory and Critical Care Medicine·Thomaz Fleury CuradoVsevolod Y Polotsky
Dec 29, 2018·Pharmaceutical Research·Gerard A RodriguesHongwen M Rivers

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Citations

Aug 5, 2020·American Journal of Respiratory and Critical Care Medicine·Sigrid Veasey
Mar 18, 2021·Respirology : Official Journal of the Asian Pacific Society of Respirology·Shane A Landry, Bradley A Edwards
Jul 3, 2021·International Journal of Molecular Sciences·Mateus R AmorimVsevolod Y Polotsky
Aug 26, 2021·Current Opinion in Pulmonary Medicine·Elisa Perger, Luigi Taranto-Montemurro

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Methods Mentioned

BETA
pharmacotherapy
transfection

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