Gene therapy for laryngeal paralysis

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.