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Potential for promoting recurrent laryngeal nerve regeneration by remote delivery of viral gene therapy

dc.contributor.authorRubin, Adam D.en_US
dc.contributor.authorHogikyan, Norman D.en_US
dc.contributor.authorOh, Alexen_US
dc.contributor.authorFeldman, Eva L.en_US
dc.date.accessioned2012-03-16T15:56:26Z
dc.date.available2013-04-01T14:17:26Zen_US
dc.date.issued2012-02en_US
dc.identifier.citationRubin, Adam D.; Hogikyan, Norman D.; Oh, Alex; Feldman, Eva L. (2012). "Potential for promoting recurrent laryngeal nerve regeneration by remote delivery of viral gene therapy ." The Laryngoscope 122(2): 349-355. <http://hdl.handle.net/2027.42/90195>en_US
dc.identifier.issn0023-852Xen_US
dc.identifier.issn1531-4995en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/90195
dc.description.abstractObjectives/Hypothesis: The aims of this study were to demonstrate the ability to enhance nerve regeneration by remote delivery of a viral vector to the crushed recurrent laryngeal nerve (RLN), to demonstrate the usefulness of a crushed RLN model to test the efficacy of viral gene therapy, and to discuss future potential applications of this approach. Study Design: Animal study. Methods: Adult Sprague‐Dawley rats were assigned to two groups. In the experimental group, an adeno‐associated viral (AAV) vector carrying a zinc‐finger transcription factor, which stimulates endogenous insulinlike growth factor I production (AAV2‐TO‐6876vp16), was injected into the crushed RLN. In the control group, an AAV vector carrying the gene for green fluorescent protein was injected into the crushed RLN. Unilateral RLN paralysis was confirmed endoscopically. At 1 week, laryngeal endoscopies were repeated and recorded. Larynges were cryosectioned in 15‐μm sections and processed for acetylcholine histochemistry (motor endplates) followed by neurofilament immunoperoxidase (nerve fibers). Percentage nerve‐endplate contact (PEC) was determined and compared. Vocal fold motion was evaluated by blinded reviewers using a visual analogue scale (VAS). Results: The difference between PEC on the crushed and uncrushed sides was statistically less in the experimental group (0.54 ± 0.18 vs. 0.30 ± 0.26, P = .0006). The VAS score at 1 week was significantly better in the experimental group ( P = .002). Conclusions: AAV2‐TO‐6876vp16 demonstrated a neurotrophic effect when injected into the crushed RLN. The RLN offers a conduit for viral gene therapy to the brainstem that could be useful for the treatment of RLN injury or bulbar motor neuron disease.en_US
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherViral Vectorsen_US
dc.subject.otherReinnervationen_US
dc.subject.otherNeurologic Diseaseen_US
dc.subject.otherAmyotrophic Lateral Sclerosisen_US
dc.subject.otherAdeno‐Associated Virusen_US
dc.subject.otherDysphoniaen_US
dc.subject.otherGene Therapyen_US
dc.subject.otherVocal Fold Paralysisen_US
dc.titlePotential for promoting recurrent laryngeal nerve regeneration by remote delivery of viral gene therapyen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelOtolaryngologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Neurology, University of Michigan, Ann Arbor, Michigan, U.S.A.en_US
dc.contributor.affiliationumLakeshore Professional Voice Center, St. Clair Shores, Michigan, University of Michigan, Ann Arbor, Michiganen_US
dc.contributor.affiliationumthe Department of Otorhinolaryngology, University of Michigan, Ann Arbor, Michiganen_US
dc.contributor.affiliationotherLakeshore Professional Voice Center, Lakeshore Ear, Nose and Throat Center, 21000 E. 12 Mile Rd., Suite 111, St. Clair Shores, MI 48081en_US
dc.identifier.pmid22241608en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/90195/1/22436_ftp.pdf
dc.identifier.doi10.1002/lary.22436en_US
dc.identifier.sourceThe Laryngoscopeen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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