SELECTIVE FUNCTIONAL RECOVERY AFTER LARYNGEAL NERVE INJURY

Washington University, Saint Louis MO

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Unilateral vocal fold paralysis (UVFP) affects over 20,000 patients annually in the US. The ideal treatment, which would restore adductor motion to the vocal fold, has not yet been developed. The long term goal of this research is to find the best treatment(s) for this problem. One idea investigated in the previous study involves a simple, pro-active approach in which one of the laryngeal muscles, the posterior cricoarytenoid (PCA), is blocked from receiving aberrant nerve growth by injecting it with vincristine, an effective nerve blocking agent. By negating the abductor function of the vocal cord, the adductor function will be free to move the vocal cord toward the midline during voicing and swallowing as it should. In this proposal a few more experiments are planned to optimize the safety of vincristine injection: reduced dosing, split dosing, and a formal toxicity study to satisfy the FDA and allow this drug to be tested in a clinical trial. Another experiment involves combining PCA vincristine injections with systemic nimodipine, in order to determine whether the combination give better adduction than either drug alone. In the second Aim, modern techniques of probing the laryngeal muscles for gene expression (using microarrays, with DNA testing for confirmation) are employed to determine what the differences are between the adductor and abductor muscles in the denervation/reinnervation process. This information can help us determine which nerve growth factors or other molecules we can use to encourage healing following injury to the laryngeal nerves. In the third Aim, a new way of delivering these nerve growth factors to the nerves that need them is investigated. This method employs acellular nerve allografts (ANAs), which are already commercially available for nerve repairs. In this study the ANAs will be loaded with growth factors in current use (GDNF, VEGF, NT-3) as well as with new factors that will be determined from Aim 2. An additional group adds Schwann cells to the ANAs, which has shown promise in similar rat studies. These three Aims are separate but related, and all of these experiments are expected to move us closer to the elusive goal of the ideal treatment for UVFP.