Gene therapy for laryngeal paralysis

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Ann Otol Rhinol Laryngol. 2007 Feb;116(2):115-22.

Gene therapy for laryngeal paralysis.

Shiotani A, Saito K, Araki K, Moro K, Watabe K.

Department of Otolaryngology-Head and Neck Surgery, National Defense

Medical College, Saitama, Japan.

OBJECTIVES: The surgical options for laryngeal paralysis only

achieve static changes of vocal fold position. Laryngeal

reinnervation procedures have had little impact on the return of

dynamic laryngeal function. The development of a new treatment for

laryngeal paralysis, aimed at the return of dynamic function and

neurologic restoration and regeneration, is necessary.

METHODS: To assess the possibility of gene therapy for laryngeal

paralysis aiming for the return of dynamic laryngeal function, we

investigated the therapeutic effects of gene therapy using rat

laryngeal paralysis models.

RESULTS: In a rat vagal nerve avulsion model, we transferred glial

cell line-derived neurotrophic factor (GDNF) gene into the nucleus

ambiguus using an adenovirus vector. Two and 4 weeks after the GDNF

gene transfer, a significantly larger number of surviving

motoneurons was observed. These neuroprotective effects of GDNF gene

transfer were enhanced by simultaneous brain-derived neurotrophic

factor gene transfer. In a rat recurrent laryngeal nerve crush

model, we transferred GDNF gene into recurrent laryngeal nerve

fibers after crush injury. Two and 4 weeks after GDNF gene transfer,

we observed significantly faster nerve conduction velocity and

better vocal fold motion recovery.

CONCLUSIONS: 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.