The MU Veterinary Health Center (VHC) is currently seeking patients for enrollment in a clinical trial for degenerative myelopathy (DM) affected dogs. The purpose of this study is to evaluate a promising new drug as a treatment for DM with hopes to slow disease progression. Dogs will be administered an antisense oligonucleotide (ASO) that will repress the production of the protein, superoxide dismutase 1 (SOD1). The ASO has been tested in a preclinical setting for safety in dogs. The drug will be injected into the spinal fluid at the low lumbar region of the spinal cord. The study will be randomized and double-blinded; neither the investigator nor the pet owner will know whether the dog receives the drug. Eight dogs will receive the drug and four dogs will receive the vehicle. Based on the randomization design, each dog has a 67 percent chance of receiving the therapy.
Please contact Joan Coates, DVM, MS, at 573-882-7821, or by email: coatesj@missouri.edu
We will monitor clinical disease progression and evaluate cerebrospinal fluid, brain MRI and muscle and nerve function. These techniques have been used extensively on ALS patients in order to monitor and predict disease progression. We would like to use these same techniques on DM-affected dogs for monitoring disease progression and to evaluate for efficacy of the drug.
Inclusion Criteria:
History
Slowly progressive loss of coordination over one-to-three months, no signs of waxing or waning, and the owners do not perceive their dog to be in discomfort
Neurologic examination
EARLY DISEASE: Progressive asymmetric general proprioceptive ataxia that is considered mild
Breeds Included
- Boxers approximately 9 years of age or older at the time of initial examination
- Pembroke Welsh Corgis approximately 10-11 years of age at the time of initial examination
- Other breeds older than 9 years old at the time of initial examination
Diagnostic Testing (Performed by a board-certified veterinary neurologist: www.acvim.org)
- No significant abnormalities on bloodwork, thoracic radiographs and abdominal ultrasound
- Genetic testing results for SOD1:c.118A mutant homozygotes (A/A – AT RISK)
- Normal entire spinal cord MRI (cervical, thoracic, lumbar, sacral)
- Normal CSF analysis
- Normal electrodiagnostic testing results
Treatments and Follow-up Testing
An informed consent will be signed by the owner and Dr. Coates. The owner must be compliant and return to the MU VHC once a month for repeat injections of the drug (under anesthesia) into the spinal fluid. Follow up electrodiagnostic testing and MRI (at MU VHC) will overlap with the treatment every three months.
Necropsy Confirmation
Following death or at time of euthanasia, the dog will need to be brought to MU VHC for necropsy. A histopathologic confirmation of DM is required.
The candidate dogs must be able to come to the University of Missouri for treatments, follow-up testing (at every three months) and at the time of euthanasia. It is simpler for participants to be within driving distance. If the first few treatments are without complications, it is possible that a board-certified veterinary neurologist located nearer to a participant’s residence will also be able to assist with therapy administration.
