02165-MOU: Identification of Biomarkers and Therapeutic Targets for Canine Degenerative Myelopathy: The Search for A Cure
Grant Status: Closed
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 proposes developing 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. The investigators 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). This work 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 grant administration and scientific progress.
Lewis, M. J., Shomper, J. L., Williamson, B. G., Vansteenkiste, D. P., Bibi, K. F., Lim, S. H. Y., Kowal, J. B., & Coates, J. R. (2021). Brain diffusion tensor imaging in dogs with degenerative myelopathy. Journal of Veterinary Internal Medicine. https://doi.org/10.1111/jvim.16248
Toedebusch, C. M., Garcia, V. B., Snyder, J. C., Jones, M. R., Schulz, D. J., Johnson, G. C., Villalón, E., Coates, J. R., & Garcia, M. L. (2019). Lumbar spinal cord microglia exhibited increased activation in aging dogs compared with young adult dogs. GeroScience. https://doi.org/10.1007/s11357-019-00133-8
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, 31(2), 513–520. https://doi.org/10.1111/jvim.14659
Toedebusch, Christine M., Snyder, J. C., Jones, M. R., Garcia, V. B., Johnson, G. C., Villalón, E. L., … Garcia, M. L. (2018). Arginase-1 expressing microglia in close proximity to motor neurons were increased early in disease progression in canine degenerative myelopathy, a model of amyotrophic lateral sclerosis. Molecular and Cellular Neuroscience, 88, 148–157. https://doi.org/10.1016/j.mcn.2018.01.009
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