Gene Therapy for Laryngeal Paralysis

Shiotani, Akiko; Saito, Koichiro; Araki, Koji; Moro, Kazuhisa; Watabe, Kazuhiko

doi:10.1177/000348940711600207

Cited by 22 publications

(22 citation statements)

References 33 publications

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“…Such recovery can only occur if RLN injury and reinnervation can be artificially influenced to occur in an ordered fashion that results in establishment of preinjury innervation patterns. To this end, much research has been focused on investigating the influence of neurotrophic factors on reinnervation and vocal fold function 1–11. An appropriate and well‐described animal model is integral to conducting this research.…”

Section: Discussionmentioning

confidence: 99%

Electromyographic and histologic evolution of the recurrent laryngeal nerve from transection and anastomosis to mature reinnervation

Pitman

Weissbrod

Roark³

et al. 2011

The Laryngoscope

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Consistent EMG, histologic, and vocal fold motion changes occur at specific time periods during RLN reinnervation after transection and anastomosis in a rat model. Reinnervation is mature at 16 weeks. Findings corroborate theories of preferential and synkinetic reinnervation after RLN transection. Use of a rat model to investigate the effect of interventions on RLN reinnervation requires a minimum of 16 weeks between transection and investigation to allow for maturation of reinnervation.

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Section: Discussionmentioning

confidence: 99%

Electromyographic and histologic evolution of the recurrent laryngeal nerve from transection and anastomosis to mature reinnervation

Pitman

Weissbrod

Roark³

et al. 2011

The Laryngoscope

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“…However, recovery of vocal fold movement is very rare, even if these procedures are performed. Vocal fold immobility after transection has the following causes: 1) motoneuron loss in the nucleus ambiguus, 2) degeneration and poor regeneration of the nerve fibers and motor end plates, 3) laryngeal muscle atrophy, and 4) misdirected reinnervation …”

Section: Introductionmentioning

confidence: 99%

Value of a novel PGA-collagen tube on recurrent laryngeal nerve regeneration in a rat model

et al. 2015

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“…However, it is difficult to retain them at injury sites because they easily diffuse. In order to maintain active concentrations, previous studies have employed multiple injections, adenoviral vectors overexpressing BDNF or GDNF, or fusion proteins such as CBD-BDNF and LBD-BDNF (3,7,13,34,35). However, the risk of surgery, immunological rejection, and costs with these methods would all be increased.…”

Section: Discussionmentioning

confidence: 99%

Brain-derived and glial cell line-derived neurotrophic factor fusion protein immobilization to laminin

Wang

Yuan

et al. 2016

Experimental and Therapeutic Medicine

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Damage to the recurrent laryngeal nerve often causes hoarseness, dyspnea, dysphagia, and sometimes asphyxia due to vocal cord paralysis which result in a reduction of quality of life. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) play critical roles in peripheral nerve regeneration. However, methods for efficiently delivering these molecules are lacking, which limits their use in clinical applications. The present study reports an effective strategy for targeting BDNF and GDNF to laminin by fusing the N-terminal domains of these molecules with agrin (NtA). More specifically, laminin-binding efficacy was assessed and sustained release assays of the delivery of BDNF or GDNF fused with NtA (LBD-BDNF or LBD-GDNF) to laminin were conducted in vitro. In addition, the bioactivity of LBD-BDNF and LBD-GDNF on laminin in vitro was investigated. LBD-BDNF and LBD-GDNF were each able to specifically bind to laminin and maintain their activity in vitro. Moreover, neurotrophic factors with NtA retained higher concentrations and bioactivity levels compared with those without NtA. The ratio of LBD-BDNF and LBD-GDNF that produced optimal effects was 4:6. BDNF and GDNF fused with NtA were effective in specifically binding to laminin. As laminin is a major component of the extracellular matrix, LBD-BDNF and LBD-GDNF may prove useful in the repair of peripheral nerve injuries.

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Gene Therapy for Laryngeal Paralysis

Abstract: These results indicate that gene therapy could be a future treatment strategy for laryngeal paralysis. Further studies will be necessary to demonstrate the safety of the vector before clinical application.

Cited by 22 publications

References 33 publications

Electromyographic and histologic evolution of the recurrent laryngeal nerve from transection and anastomosis to mature reinnervation

Electromyographic and histologic evolution of the recurrent laryngeal nerve from transection and anastomosis to mature reinnervation

Value of a novel PGA-collagen tube on recurrent laryngeal nerve regeneration in a rat model

Brain-derived and glial cell line-derived neurotrophic factor fusion protein immobilization to laminin

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