Vocal cord paralysis occurs when nerve impulses to the larynx are disrupted, causing problems with speech and breathing. Vocal cord closure is crucial for the production of sound, or phonation, and to protect the airway from food and liquids that might enter.
The nerve to the vocal cords can be injured in a variety of ways, including surgical injury (especially thyroid surgery), tumors and viral infections. If one vocal cord becomes paralyzed, the voice is soft and breathy and it may be difficult to swallow due to aspiration of thin liquids. If both vocal cords are involved, they will not open for breathing and many patients require a tracheotomy.
Randal C. Paniello, MD, PhD“Although we have many treatment options for these problems, none of these options currently restore normal vocal cord function,” says Randal Paniello, MD, professor of head and neck surgery. “Our research seeks to find new and better ways to treat paralyzed vocal cords.”
According to Dr. Paniello, adult muscle stem cells (MSCs), implanted into a muscle that has lost its nerve, can improve muscle function, in part by regrowth of the nerve for that muscle. His lab is now testing the use of muscle stem cells in an animal model of laryngeal nerve injury.
The experimental procedure is straightforward. They measure normal baseline (pre-treatment) muscle strength in the animal, then cut and repair the laryngeal nerve. At the same time, a small muscle sample is collected from which some MSCs can be isolated. These cells are cultured to a suitable volume over 6-8 weeks and then implanted into the laryngeal muscle of interest, the primary muscle that either opens or closes the vocal cord.
After a few months of healing, strength of the laryngeal muscles is measured again and compared with the baseline measure. The desired outcome is restoration of nerve function, but nerves grow slowly, so it takes several months to know whether or not an intervention has helped. In spite of that some progress has been made in documenting the levels of recovered function in both control and experimental animals.
“In control animals, without any stem cells, nerve function typically recovers to about 60% of baseline,” says Dr. Paniello. “Implanting MSCs into the vocal cord closing muscles improves that functional recovery to 128% of baseline. Implanting MSCs into the opening muscles also showed enhanced improvement, up to 83% of normal.”
Former resident Dr. Neel Bhatt discusses laryngeal nerve reinnervation during a recent symposium.The studies are not without significant hurdles to overcome. The biggest challenge says Dr. Paniello is obtaining funding. Experiments take around six months, and research animals with their daily care are expensive. A new NIH grant application is pending review.
Dr. Paniello has been assisted by residents and other collaborators. Dr. Andrea Park and Dr. Neel Bhatt were residents that worked on these experiments during their T32 research time. Dr. Stacy Halum is a laryngologist at Purdue University who grows MSCs from muscle samples the lab provides. Dr. Aaron Johnson is a stem cell researcher at Washington University that will collaborate on future studies of cellular mechanisms of laryngeal muscle recovery, when funding is obtained.
To learn more about these or other studies being conducted by the Paniello lab, please contact Dr. Randal Paniello at paniellor@wustl.edu.