This work is the 2010 Triological Thesis of Adam D. Rubin, MD.
Laryngology: Triological Society Candidate Thesis
Article first published online: 12 JAN 2012
Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.
Volume 122, Issue 2, pages 349–355, February 2012
How to Cite
Rubin, A. D., Hogikyan, N. D., Oh, A. and Feldman, E. L. (2012), Potential for promoting recurrent laryngeal nerve regeneration by remote delivery of viral gene therapy. The Laryngoscope, 122: 349–355. doi: 10.1002/lary.22436
This work was supported by the A. Alfred Taubman Medical Research Institute, the Program for Neurology Research and Discovery, and a grant from the ALS Association. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
- Issue published online: 23 JAN 2012
- Article first published online: 12 JAN 2012
- Accepted manuscript online: 7 NOV 2011 11:00AM EST
- Manuscript Accepted: 13 OCT 2011
- Manuscript Revised: 6 OCT 2011
- Manuscript Received: 29 JUL 2011
- Gene therapy;
- viral vectors;
- vocal fold paralysis;
- neurologic disease;
- amyotrophic lateral sclerosis;
- adeno-associated virus;
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.
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).
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).
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.