Laryngeal paralysis usually occurs as a result of the surgical removal of tumor involving the head and neck region and skull base. Thyroid surgery, carotid endarterectomy, cardiothoracic and primary lung procedures may also result in laryngeal paralysis. Patients with laryngeal paralysis typically present with disabling symptoms including loss of voice, difficulty swallowing and airway obstruction. While surgical procedures exist to remedy these symptoms, their success has been limited by the muscle atrophy that accompanies laryngeal paralysis. Moreover, current approaches to the surgical repair of injured nerves have had little impact on return of laryngeal function and are not widely accepted as treatment options. To address this clinical problem, we have designed a rat laryngeal paralysis model to study novel gene transfer strategies using a muscle specific expression system to enhance local delivery of growth factors. In preliminary studies, a non-viral vector containing the a-actin promoter and human IGF-I gene sequence was injected into paralyzed adult rat laryngeal muscle. Positive effect on both muscle and nerve were demonstrated one month following single injection of this hIGF-I gene formulation. These effects were comparable to those observed following daily, local or systemic, injections with hIGF-I protein given over 3 to 6 weeks. Base on preliminary findings, it is hypothesized that the myotrophic and neurotrophic effects of hIGF-1 will have greater impact during the process of nerve regeneration and muscle reinnervation. This study will explore the use of non-viral and viral gene transfer for the delivery of hIGF-I and other growth factors applied to reinnervation of laryngeal muscle. Our results will have direct relevance towards creating a more practical treatment strategy for human disorders, including treatment of laryngeal paralysis and other peripheral nerve injuries.
