2165: Identification of Biomarkers and Therapeutic Targets for Canine Degenerative Myelopathy: The Search for A Cure

Grant Status: Open

Grant Amount: $154,077
Dr. Joan R. Coates, DVM, University of Missouri, Columbia
January 1, 2015 - December 31, 2016
Sponsor(s): American Boxer Charitable Foundation
Breed(s): Boxer
Research Program Area: Neurology

Abstract

Degenerative myelopathy (DM) is an adult onset disease of the spinal cord causing progressive weakness and paralysis of the hind limbs and eventually all limbs. Mutations in an enzyme that converts superoxide to water and hydrogen peroxide, superoxide dismutase 1 (SOD1), have been linked to DM and amyotrophic lateral sclerosis (ALS-Lou Gehrig's disease). DM is associated with degenerative loss of axons, which transmit signals from the brain and spinal cord to their targets (muscle). Currently no diagnostic test exists that would allow for repeated measurements with minimal invasiveness. Dr. Coates is proposing to develop a test that would assay the blood and cerebrospinal fluid (CSF) for proteins that are exclusively found in axons under non-disease conditions, referred to as neurofilament proteins. They will correlate the concentrations of neurofilament proteins in CSF and blood with disease stage, and anticipate that neurofilament protein concentration in blood and CSF will increase as disease progresses. Such a test will allow for minimally invasive monitoring of disease. Furthermore, such a diagnostic test could be used to measure the success of therapy, which may be underway in a cohort of DM-affected dogs [Boxers and Pembroke Welsh Corgis (PWC)] (funded by NIH/NINDS). They will complement the test for neurofilament proteins with other studies that measure disease progression such as specific MRI techniques to evaluate the brain and spinal cord and electrical testing of the muscle and nerves. These are functional disease markers that are also being studied in ALS patients. Funding for the research is provided through the efforts and generosity of the American Boxer Charitable Foundation. The AKC Canine Health Foundation supports the funding of this effort and will oversee administration of funds and scientific progress reporting.

Publication(s)

Toedebusch, C. M., Bachrach, M. D., Garcia, V. B., Johnson, G. C., Katz, M. L., Shaw, G., … Garcia, M. L. (2017). Cerebrospinal Fluid Levels of Phosphorylated Neurofilament Heavy as a Diagnostic Marker of Canine Degenerative Myelopathy. Journal of Veterinary Internal Medicine, n/a-n/a. http://doi.org/10.1111/jvim.14659

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