Gene Therapy for Recurrent Laryngeal Nerve Injury

Abstract

Recurrent laryngeal nerve (RLN) injury has considerable clinical implications, including voice and swallowing dysfunction, which may considerably impair the patient’s quality of life. Recovery of vocal fold movement is an essential novel treatment option for RLN injury. The potential of gene therapy for addressing this issue is highly promising. The target sites for RLN gene therapy are the central nervous system, nerve fibers, laryngeal muscles, and vocal cord mucosa. Gene transduction has been reported in each site using viral or non-viral methods. The major issues ensuing after RLN injury are loss of motoneurons in the nucleus ambiguus, degeneration and poor regeneration of nerve fibers and motor end plates, and laryngeal muscle atrophy. Gene therapy using neurotrophic factors has been assessed for most of these issues, and its efficacy has been reported. Another important matter for functional vocal fold movement recovery is misdirected regeneration, in which the wrong neurons may innervate other laryngeal muscles, where even if innervation is reestablished, proper motor function is not restored. Novel strategies involving gene therapy bear promise for overcoming this issue and further investigations are underway.

Keywords

• gene therapy
• recurrent laryngeal nerve
• vocal fold
• misdirected reinnervation
• neurotrophic factor
• adenovirus
• adeno-associated virus
• Sendai virus
• non-viral gene delivery
• electroporative gene delivery