Degenerative Myelopathy Benelli’s Story by Lauren Meadows

1. Degenerative MyelopathyBenelli’s Story by Lauren Meadows

2. Agenda Videos What is DM? Occurrences & Causes Clinical Signs & Progression Diagnosis Prevention Through Ethical Breeding Genetic Classifications Highlights References

3. Benelli – Declined Mobility Taken approximately 1 month after we noticed a significant decline in his mobility. His hind feet are knuckling over and he is dragging his toes. http://youtu.be/H2DlSN9OKoE

4. 1 month later… Very little improvement even after physiotherapy, various medications and chiropractic. Benelli is wearing “boots” for added traction, it was the only way he could walk indoors. He has little muscle coordination resulting in unsteady gait and has loss of hind end awareness when he sits. http://youtu.be/oYiDQ8sdOI8

5. What is Degenerative Myelopathy? • A progressive disease of the spinal cord • Causes demyelination (loss of insulating coating) and axonal loss (loss of nerve fibers)1 • The end result is paralysis and loss of sensation in the limbs within 6 months to 1 year of symptoms • Larger breeds are more likely to be afflicted 1[University of Missouri-Columbia College of Veterinary Medicine] http://genericlook.com/img/uploads/anatomy/myelination.jpg

6. DM Occurrence and Cause(s) • Disease is more likely to affect larger dog breeds: • German Shepherds, Boxers, Rhodesian Ridgeback, Belgium Shepherd, Old English Sheep Dog, Weimaraner • Though it can be found in others (Corgi, Pugs, Terriers) • Average age of onset is between 7 and 14 years • The exact cause is unknown • May be due to an autoimmune disease similar to Multiple Sclerosis in humans • Has been linked to a gene mutation which causes Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig’s disease) in humans.

7. Clinical Signs and Progression Most commonly begins as a lack of muscle coordination especially in hind legs: Crossing over hind legs Dragging toes Knuckling over

8. Diagnosis • There are no specific tests that will confirm DM • It is often diagnosedthrough the process of elimination: • If lab work, X-ray, MRI, do not identify another disease than DM is assumed. • The only way to confirm the diagnosis is an autospsy, when the spinal cord can be examined under the microscope. • Thus it can be possible to prevent the spread of this disease through selective breeding and genetic testing

9. Prevention Through Breeding • Because DM is a genetic trait, testing and breeding may significantly decrease the risk of DM • Testing can be easily performed by a DNA sample sent to the Orthopedic Foundation for Animals (OFA) in collaboration with the University of Missouri. There are others labs that offer similar buccal swab testing made available to the public. • The specific gene is the SOD1 mutation • Dogs can be identified as Normal, Carrier or At Risk

10. Genetic Classifications • If a dog carries two normal copies of the gene (NORMAL) • Highly unlikely to develop DM • Highly unlikely to pass on the disease to any offspring. • If a dog has one mutated copy and one normal copy (CARRIER) • Highly unlikely to develop DM • Can transmit mutated gene to it’s offspring • If adog has two mutated copies of the gene, it is at risk for and likely of developing DM, and has a 50/50 chance of producing Carrier and At Risk offspring.

11. Highlights • Degenerative Myelopathy is a crippling disease that has no cure and is lethal • The occurrence of DM may be reduced through genetic testing and selective breeding • As a breeder: test your breeding dogs • As an owner, ask your breeder whether this testing had been completed and what were the results

12. References • Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis TomoyukiAwano, Gary S. Johnson, Claire M. Wade, Martin L. Katz, Gayle C. Johnson, Jeremy F. Taylor, Michele Perloski, Tara Biagi, IzabellaBaranowska, Sam Long, Philip A. March, Natasha J. Olby, G. Diane Shelton, Shahnawaz Khan, Dennis P. O'Brien, Kerstin Lindblad-Toh, Joan R. Coates. ProcNatlAcadSci U S A. 2009 February 24; 106(8): 2794–2799. Published online 2009 February 2. doi: 10.1073/pnas.0812297106 PMCID: PMC2634802 • Degenerative Myelopathy German Shepherd Dogs: R.M. Clemmons, DVM, PhD Associate Professor of Neurology & Neurosurgery Small Animal Clinical Sciences. • Degenerative Myelopathy in Dogs Canine Genetic Disease Network: DrJoan Coates and Dr Gary Johnson and associates at the University of Missouri-Columbia College of Veterinary Medicine. • Canine DM – Update on Diagnosis and Therapy. Presented by Joan R. Coates, DVM, MS, Diplomate ACVIM (Neurology), Associate Professor, Department of Veterinary Medicine and Surgery, University of Missouri • Eddie Dziuk of OFA and the Animal Molecular Genetics Laboratory (Gary Johnson and Liz Hansen) and the work being done by the University of Missouri (Coates and Colleagues) and the Broad Institute of MIT/Harvard (Drs. Lindblad-Toh and Wade)

13. In Memory of Benelli Born a dog, died a gentleman.