{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:20:08Z","timestamp":1787077208304,"version":"build-2736575974"},"reference-count":61,"publisher":"SAGE Publications","issue":"15-16","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2020,8]]},"abstract":"\n Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by degeneration of motor neurons and muscles, and death is usually a result of impaired respiratory function due to loss of motor neurons that control upper airway muscles and\/or the diaphragm. Currently, no cure for ALS exists and treatments to date do not significantly improve respiratory or swallowing function. One cause of ALS is a mutation in the superoxide dismutase-1 (\n SOD1<\/jats:italic>\n ) gene; thus, reducing expression of the mutated gene may slow the progression of the disease. Our group has been studying the\n SOD1<\/jats:italic>\n G93A<\/jats:sup>\n transgenic mouse model of ALS that develops progressive respiratory deficits and dysphagia. We hypothesize that solely treating the tongue in\n SOD1<\/jats:italic>\n mice will preserve respiratory and swallowing function, and it will prolong survival. At 6 weeks of age, 11\n SOD1<\/jats:italic>\n G93A<\/jats:sup>\n mice (both sexes) received a single intralingual injection of gene therapy (AAVrh10-miR\n \n SOD1<\/jats:italic>\n <\/jats:sup>\n ). Another 29 mice (both sexes) were divided into two control groups: (1) 12\n SOD1<\/jats:italic>\n G93A<\/jats:sup>\n mice that received a single intralingual vehicle injection (saline); and (2) 17 non-transgenic littermates. Starting at 13 weeks of age, plethysmography (respiratory parameters) at baseline and in response to hypoxia (11% O\n 2<\/jats:sub>\n ) + hypercapnia (7% CO\n 2<\/jats:sub>\n ) were recorded and videofluoroscopic swallow study testing were performed twice monthly until end-stage disease. Minute ventilation during hypoxia + hypercapnia and mean inspiratory flow at baseline were significantly reduced (\n p<\/jats:italic>\n \u2009<\u20090.05) in vehicle-injected, but not AAVrh10-miR\n \n SOD1<\/jats:italic>\n <\/jats:sup>\n -injected\n SOD1<\/jats:italic>\n G93A<\/jats:sup>\n mice as compared with wild-type mice. In contrast, swallowing function was unchanged by AAVrh10-miR\n \n SOD1<\/jats:italic>\n <\/jats:sup>\n treatment (\n p<\/jats:italic>\n \u2009>\u20090.05). AAVrh10-miR\n \n SOD1<\/jats:italic>\n <\/jats:sup>\n injections also significantly extended survival in females by \u223c1 week. In conclusion, this study indicates that intralingual AAVrh10-miR\n \n SOD1<\/jats:italic>\n <\/jats:sup>\n treatment preserved respiratory (but not swallowing) function potentially\n via<\/jats:italic>\n increasing upper airway patency, and it is worthy of further exploration as a possible therapy to preserve respiratory capacity in ALS patients.\n <\/jats:p>","DOI":"10.1089\/hum.2020.065","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T03:04:21Z","timestamp":1591326261000},"page":"828-838","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Intralingual Administration of AAVrh10-miR\n \n SOD1<\/i>\n <\/sup>\n Improves Respiratory But Not Swallowing Function in a Superoxide Dismutase-1 Mouse Model of Amyotrophic Lateral Sclerosis"],"prefix":"10.1177","volume":"31","author":[{"given":"Lori A.","family":"Lind","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellyn M.","family":"Andel","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela L.","family":"McCall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin S.","family":"Dhindsa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia E.","family":"Stricklin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Mueller","sequence":"additional","affiliation":[{"name":"Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA"},{"name":"Department of Pediatrics, University of Massachusetts Medical School, Worcester Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai K.","family":"ElMallah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa E.","family":"Lever","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Missouri, 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