title: Potential for promoting recurrent laryngeal nerve regeneration by remote delivery of viral gene therapy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Lakeshore Professional Voice Center, St. Clair Shores, Michigan, University of Michigan, Ann Arbor, Michigan 48081, USA. Rubinad1968@gmail.com
authors.forename: Adam D
authors.initials: AD
authors.lastname: Rubin
authors.forename: Norman D
authors.initials: ND
authors.lastname: Hogikyan
authors.forename: Alex
authors.initials: A
authors.lastname: Oh
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
mesh_terms: D000818:Animals; D000229:Dependovirus; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D007267:Injections; D007828:Laryngoscopy; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012009:Recurrent Laryngeal Nerve / Q000502:physiology*; D016896:Treatment Outcome; D014826:Vocal Cord Paralysis / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D014827:Vocal Cords