Gene Therapy

Vocal fold paralysis therapies

A collaboration between PNR&D scientists and surgeons from the Otolaryngology-Head and Neck Surgery Department and the Department of Neurology focuses upon the problem of paralysis affecting the vocal folds. Vocal fold paralysis is a problem that can occur following nerve injury after surgery, from tumors, or spontaneously from an unknown cause. Paralysis of one of the paired vocal folds can cause severe voice and swallowing problems, and if both vocal folds are paralyzed, breathing usually becomes difficult. There are no treatments available to cure vocal fold paralysis and restore proper vocal fold movement. Current treatment options only provide static solutions that help patients compensate for the lost function in order to improve voice and swallowing problems. While this approach achieves improvements in the patients’ ability to communicate, it does not typically produce perfect results. Furthermore, very few treatment options exist for patients with paralysis of both vocal folds that provide both good voice outcomes and adequate airway support.

A laboratory model of vocal fold paralysis has been developed in order to study vocal fold paralysis and develop treatments. The PNR&D has used this model to investigate novel treatment approaches, including virally-mediated gene therapy, reinnervation using muscles and nerves from the non-paralyzed side, and exploration of the body’s own natural ability to spontaneously restore mobility of the vocal folds. Understanding the natural process of reinnervation and how to activate and harness this process following chronic vocal fold paralysis will allow for the development of better treatment options for patients.

Gene therapy for vocal fold paralysis

A common hurdle to the treatment of vocal fold paralysis is the inability to effectively target therapies to the nerves controlling vocal fold movement. To overcome this hurdle, PNR&D investigators are currently developing and optimizing gene therapy approaches to deliver neuroprotective factors to the nervous system. Gene therapy involves the delivery of genetic material (DNA or RNA) that carries the code for helpful proteins to damaged tissues, where cells can take up the genetic material and begin production of the specific proteins that may support their survival and repair. Using genetically engineered viruses, genes for neural growth factors can be injected into muscles, where they are then taken up by the neuron axons that form connections to the muscles and are transported to the cell bodies of the neurons inside the spinal cord. Growth factors like insulin-like growth factor-I (IGF-I) elicit neuroprotective properties in both cellular and animal models of nerve injury and can be specifically delivered to neurons using this approach. Similarly, vectors delivering a transcription factor designed to upregulate the neuroprotective growth factor vascular endothelial growth factor (VEGF) have also been successfully developed and are currently being tested in various disease and injury models. Results of ongoing gene therapy techniques in the PNR&D are anticipated to provide a novel, minimally invasive means to administer and target therapies to degenerating neurons during vocal fold paralysis.