Canine Degenerative Myelopathy: Pathophysiology and Clinical Trial

Presentation Description / Summary: Canine degenerative myelopathy (DM) is an adult-onset spinal cord disease causing progressive paresis and paralysis in the pelvic limbs and eventually all limbs. The earliest clinical sign of canine DM is general proprioceptive ataxia in the pelvic limbs. We will describe the neuropathology of the general proprioceptive pathway with emphasis on single-nucleus RNA sequencing of the dorsal root ganglion (DRG). A hallmark of CNS tissues in dogs with DM is loss of the excitatory amino acid transporter (EAAT2), which causes failure of glutamate uptake and leads to excitotoxicity and neuron death. We are evaluating riluzole, a glutamate antagonist, approved for the treatment of human amyotrophic lateral sclerosis (ALS), in dogs with DM. The long-term goal of our group is to establish effective clinical strategies for treatment of canine DM through the efficient conduct of veterinary clinical trials. Toward this goal, our group has recently worked to establish a collaborative network of canine DM researchers (Project DM), designed and implemented a longitudinal DM patient registry to enhance data collection and observational studies, and built a platform trial design which can serve as perpetual infrastructure through which to evaluate novel therapies and biomarkers.