Accelerating Recovery After Laryngeal Nerve Graft in Horses
Principal Investigator: Jonathan Cheetham
DESCRIPTION (provided by applicant):
Recurrent laryngeal neuropathy (RLN) or “Roaring” is a major cause of poor athletic performance affecting 8% of racehorses and a higher percentage of sport horses. RLN produces axonal loss with demyelination and subsequent loss of cricoarytenoid dorsalis (CAD) muscle volume and inability to maintain an open airway. A surgical solution that maintains airflow by preserving CAD muscle mass and function would be associated with improved performance outcomes. A number of nerve-muscle pedicle graft techniques have been used in an attempt to restore function of this muscle. These methods transfer an innervating nerve into a small region of a denervated muscle. As they only innervate a small portion of the muscle, recovery is slow and limited and this approach has not yet gained widespread acceptance.
In this proposal we use a reinnervation approach combined with immunomodulation at the surgery site. Performing a nerve anastomosis (graft), we would take advantage of the existing architecture of the recurrent laryngeal nerve to reach all the portions of the CAD muscle, which opens the larynx. Alone, this should produce much faster recovery than nerve-muscle pedicle graft as we use the existing network of the distal RLn to guide reinnervating axons to the CAD muscle. We also intend to modulate the microenvironment at the site of nerve graft to test the hypothesis that immunomodulation will further improve the recovery time. We have used this approach in dogs and shown return of function by 7 weeks after repair. If successful in horses, this approach would be a very large improvement on existing techniques.
To modify the nerve microenvironment, we focus on the use of interleukin-10 (IL-10), a cytokine with known anti-inflammatory and immunomodulatory effect. We have already obtained strong preliminary data which support this approach.
If successful, we are in a position to immediately translate these approaches to horses affected by RLN in a clinical trial of client horses with grade III recurrent laryngeal neuropathy.