Riluzole as a Neuroprotectant in Canine Degenerative Myelopathy
Please note the patient needs to be within driving distance of one of the four trial sites and be reevaluated by the trial site a specified times.
Canine degenerative myelopathy (DM) is an adult-onset spinal cord disease causing progressive paresis and paralysis of the pelvic limbs and eventually all limbs. To date, no therapy has been shown to slow the clinical progression of DM. A hallmark of CNS tissues in dogs with DM is loss of the excitatory amino acid transporter (EAAT2). Loss of EAAT2 causes failure of glutamate uptake, which leads to excitotoxicity and neuron death. This grant will evaluate riluzole, a glutamate antagonist, approved for the treatment of human amyotrophic lateral sclerosis (ALS), in dogs with DM. The long-term goal of our group is to establish effective clinical strategies for treatment of canine DM through the efficient conduct of veterinary clinical trials. Toward this goal, our group has recently worked to establish a collaborative network of canine DM researchers (Project DM), designed and implemented a longitudinal DM patient registry to enhance data collection and observational studies, and built a platform trial design which can serve as perpetual infrastructure through which to evaluate novel therapies and biomarkers. We hypothesize that riluzole, at an optimized dose, will delay disease progression, as evidenced by alteration of both disease-associated biomarkers and clinical outcome measures, therefore improving overall longevity and quality of life in dogs with DM. We will test this hypothesis through the following aims: 1) evaluate oral riluzole safety and establish a candidate dose; 2) conduct a clinical trial for therapeutic efficacy; and 3) demonstrate that neurofilament light concentrations in CSF and plasma are a valuable biomarker.
Aim 1: Evaluate oral riluzole safety and establish a candidate dose in a small number of dogs affected with DM.
Inclusion criteria will include DM affected dogs at any disease stage with normal physical examination, no significant findings on bloodwork and urinalysis and not being administered medications that will alter hepatic metabolism (i.e., antiseizure drugs).
Aim 2: Conduct a clinical trial for therapeutic efficacy of oral riluzole treatment in dogs with DM.
Inclusion Criteria: Twenty healthy dogs affected with DM will be enrolled once required inclusion criteria are met: homozygosity for SOD1:c. 118G>A, early disease signs (general proprioceptive ataxia, mild ambulatory paraparesis, gait score < 3), normal health screen (CBC, chemistry profile, urinalysis, thoracic radiographs, abdominal ultrasound), elimination of other neurologic diagnoses based off findings of the thoracic and lumbar spinal cord MRI, CSF analysis and electromyography, and completion of the informed consent document. Histopathology of the spinal cord ultimately will confirm the diagnosis of DM at the time of the dog’s death/euthanasia.
Exclusion Criteria: Dogs will be excluded if there is a co-morbidity with a poor prognosis or if co-morbidity (e.g., orthopedic disease) affects the neurologic examination apart from signs of DM. If there are significant compressive lesions on MRI that confound a DM diagnosis, the dog will be excluded. Other reasons for exclusion include owner unable to follow proposed rechecks/treatments and return their dog to the trial site for necropsy diagnosisMore Information
Name: Joan R. Coates (Co-PIs: Sarah Moore, Dominik Faissler, Natasha Olby)
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Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.