“Canine Degenerative Myelopathy: From Gene Mutation Discovery to Clinical Trials”
Presented by Joan R. Coates, DVM, MS, Diplomate ACVIM (Neurology)
Original air date: October 17, 2019
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Canine degenerative myelopathy (DM) is a progressive neurodegenerative disease with a late age of onset and no known treatment. Histopathology of the central nervous system (spinal cord) is required for definitive diagnosis. Since this is not possible in a living patient, a clinical diagnosis of DM is made by a diagnosis of exclusion – meaning concurrent diseases and those that cause similar clinical signs must be ruled out, leaving DM as the most likely cause for symptoms.
AKC Canine Health Foundation (CHF) funded research in the laboratories of Drs. Coates and Gary Johnson at the University of Missouri and Drs. Kerstin Lindblad-Toh and Claire Wade of the Broad Institute at MIT/Harvard showed in a GWAS study a high association on canine chromosome 31 in the gene that encodes for superoxide dismutase 1 (SOD1).1 However, not every dog that is homozygous for this mutation has gone on to develop disease, indicating that additional genetic and/or environmental factors and random effects may influence disease development. Researchers later found such a disease modifier gene mutation (affecting the production of SP110 nuclear body protein) that strongly affects overall disease risk and is associated with an earlier age of onset specifically in Pembroke Welsh Corgis.2
Despite these advances, there is still no large-scale data regarding the risk of disease for dogs with any combination of these genetic mutations. Therefore, Dr. Coates provides the following guidance for interpreting DM genetic test results:
- Testing positive for an ‘at risk’ mutation means that the dog is at risk for developing clinical signs of DM at some point in their life.
- However, the variable and late age of onset for DM means that not all ‘at risk’ mutation positive dogs will develop DM. Other significant health concerns may occur before any clinical signs of DM.
- Eliminating all dogs from the gene pool that test positive for an ‘at risk’ mutation will significantly limit the genetic diversity of a breed and increase the risk of other diseases becoming more common in the subsequently limited gene pool.
- It is imperative to get a definitive diagnosis through pathological examination of the spinal cord. Moreover, the pet owner needs to collaborate with their primary care veterinarian and veterinary neurology specialist to get an appropriate diagnosis in order to rule out other diseases that mimic DM.
The future of canine degenerative myelopathy research includes the ongoing search for modifier gene mutations and the continued study of various biomarkers that may be targets for pre-mortem diagnostic tests or treatments. You can help support these efforts by donating to the AKC Canine Health Foundation at www.akcchf.org/donate.
- Awano, T., Johnson, G. S., Wade, C. M., Katz, M. L., Johnson, G. C., Taylor, J. F., … Coates, J. R. (2009). Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences, 106(8), 2794–2799. https://doi.org/10.1073/pnas.0812297106
- Ivansson, E. L., Megquier, K., Kozyrev, S. V., Murén, E., Körberg, I. B., Swofford, R., … Lindblad-Toh, K. (2016). Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy. Proceedings of the National Academy of Sciences, 113(22), E3091–E3100. https://doi.org/10.1073/pnas.1600084113
- 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