Vocal fold paralysis affects 120,000 people in the US – sometimes with devastating consequences to simple tasks like breathing, swallowing and speech. Professor of Otolaryngology Randal Paniello, MD, PhD, is exploring a novel stem cell treatment that may offer hope for reinnervation of the affected muscles.
Vocal fold paralysis refers to the loss of neural control over the muscles that control the voice. Opening or abduction of the vocal folds is essential for proper breathing. Closure or adduction of the folds allows them to vibrate and produce sound as air is forced between them. Closure also protects the airway during swallowing.
Paralysis can be due to several causes including neck injury, stroke, tumors, infections and neurological diseases. Damage to the recurrent laryngeal nerve during thyroid or parathyroid gland surgery is likely the most common cause of vocal fold paralysis.
According to Paniello, laryngeal muscle atrophy starts within weeks of nerve damage and progresses for months following. Muscle damage is considered irreversible after about 15-18 months. Some spontaneous recovery may occur between six and 12 months post injury and can give a general idea of prognosis. Depending on severity of the injury, treatment can range from voice therapy to surgery to help medialize the vocal folds. Cases of acute bilateral nerve damage may require a tracheostomy, the surgical creation of an opening to the windpipe to allow breathing. Regardless, current treatments for vocal folds paralysis are considered suboptimal as they involve foreign body implants or are destructive of the vocal mechanism.
Could stem cells provide the answer?
Muscle progenitor cells or myosatellite cells are a stem cell found in adult muscle that can replicate to give rise to myoblasts, a precursor to a skeletal muscle cell. These myoblasts can then fuse with their parent muscle cells or generate new cells to increase the size of a muscle.
Recent studies done by the Paniello Lab and others have shown that these progenitor cells can be isolated from a healthy skeletal muscle, cultured, and implanted back into denervated laryngeal muscles, where they become incorporated into the muscle. Pilot studies in the lab have shown this technique useful for enhancing nerve recovery in addition to increasing muscle bulk and strength.
Specific aims of the current study are twofold:
- Repeat pilot studies using treatment delays of three months and six months from the time of nerve injury, to better mimic the human condition. The number of progenitor cells implanted will be varied to find the optimum number. These results will provide data needed for a possible clinical trial. These experiments will utilize a canine model to best simulate the size, volume and function of human laryngeal muscles.
- Explore the cellular and molecular mechanisms underlying progenitor cell stimulation of reinnervation. The team will use bulk RNA sequencing and mass spectrometer imaging to identify peptides or other potentially neurotrophic molecules that are increased following progenitor cell implants.
Paniello and recently hired Staff Scientist Chang Gui, PhD, hope these studies will ultimately provide support for clinical trials. If successful, the approach will be capable of restoring activity to the paralyzed vocal fold muscles to allow for satisfactory voice, swallowing and breathing without damage to the vocal folds.
The work is supported by a five-year, $3.5 million NIH R01 award. For more information on these studies, please contact Randal Paniello, MD, PhD, at paniellor@wustl.edu.