Displaying results 1 - 10 of 76 items found.
(Web Page; Tue Apr 15 15:26:00 CDT 2014)
Description: Genetic test for Degenerative Myelopathy risk factor.
2. Research Spotlight: Degenerative Myelopathy
(Web Page; Thu Mar 09 10:23:00 CST 2017)
Description: Learn how your investment is making an impact on Degenerative Myelopathy.
3. Identification of Genetic Risk Factors in Degenerative Myelopathy in German Shepherd Dogs
(Web Page; Thu Dec 30 11:16:00 CST 2021)
Description:
Canine degenerative myelopathy (DM) is an adult-onset neurodegenerative disease that causes a progressive loss of spinal cord function and typically culminates with euthanasia. In the 1970s, DM was considered to be a disease of German Shepherds Dogs. We now know that DM occurs in many other breeds; nonetheless, DM remains a significant cause of disease and premature death in German Shepherd Dogs. In cooperation with the German Shepherd Dog Club of America, Dr. Kerstin Lindblad-Toh, from the Broad Institute, is working to determine if there are as yet undiscovered factors in the genetic background of German Shepherd Dogs that make them more or less susceptible to the development of DM.
Participation Requirements:
Phase 1
Drs. Gary Johnson and Joan Coates at the University of Missouri are assisting Dr. Kerstin Lindblad-Toh with sample collection for this project. In the first phase of this project, they are seeking cheek-swab samples from purebred German Shepherd Dogs that are
- six years old or older,
- have not already had a DNA test for the DM-associated mutation, and
- are free from musculoskeletal disease as indicated by a normal (limp-free) gait.
If you are willing to donate a cheek swab (or blood) sample from one or more of your healthy German Shepherd Dogs, please download and fill out a form for each dog and email them along with a scan of your dog’s pedigree to Liz Hansen (HansenL@missouri.edu) Specifically, we are requesting the following information:
- the dog's birth date,
- the dog's registration number,
- and a copy of the dog's pedigree.
Phase 2
Based on the age and pedigree information provided in the form, we will select approximately 400 dogs that together best represent the entire German Shepherd Dog population. Kits with cheek swabs and instructions for cheek-swab collection will be sent to the owners of the selected dogs. We will isolate DNA from the returned cheek swabs and test for the mutation responsible for degenerative myelopathy. Confidential test results will be emailed, without charge, to the owners of the selected dogs. The results of this first phase of this project will help us fine tune subsequent phases and maximize our chances for finding as yet undiscovered factors in the genetic background of German Shepherd Dogs that make them more or less susceptible to the development of DM.
The DNA from these cheek swabs will be tested for the SOD1 risk allele and used in subsequent experiments to identify genetic factors that modify the ages at onset or the rate of progression of DM in GSD.
(Web Page; Wed Jul 01 11:27:00 CDT 2020)
Description:
The purpose of this study is to study the disease progression of degenerative myelopathy in dogs. We will further characterize the disease features in the central (spinal cord and brain) and peripheral nervous systems. DNA will be banked and pedigree data collected from affected dogs and family members while maintaining anonymity so that it will be available for future gene mapping studies.
Participation:
Dogs with a presumptive diagnosis of DM as established by conventional diagnostic evaluations (myelography / special imaging (MRI) of the spine) at the MU Veterinary Health Center or another referral hospital will be considered for the study.
Your dog’s participation in this study will consist of a necropsy examination (i.e., apostmortem examination of internal organs).
Owner's Responsibilities:
A thorough examination of your dog’s spinal cord, brain and nerves, at the time of death is necessary to confirm the diagnosis of degenerative myelopathy and to identify any co-existing disease. After the necropsy (i.e., visual examination) is completed, your dog will be cremated. If the necropsy is performed at the MU VHC, we can make special arrangements for an individual private cremation. Microscopic examination of tissue samples collected during the necropsy will be done subsequently and you will receive the results of the final diagnosis. Tissues will also be stored appropriately and made available to other laboratories/researchers for additional studies of DM.
Access the client consent form here to learn more about this study,
5. Riluzole as a Neuroprotectant in Canine Degenerative Myelopathy
(Web Page; Thu May 25 10:52:00 CDT 2023)
Description:
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.
Participation Requirements
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 diagnosis
6. Mapping of Additional Genes Associated with Canine Degenerative Myelopathy
(Web Page; Fri Aug 16 11:20:00 CDT 2019)
Description:
Background: Degenerative myelopathy (DM) is a fatal disease of the spinal cord causing progressive paralysis in mature dogs. In grant 821 these researchers performed genome-wide association mapping and identified an SOD gene mutation which is present in many breeds. A DNA test can now identify dogs at risk of developing DM, although many dogs that have the mutation never develop clinical symptoms. The availability of the DM test has raised questions that must be answered before the test can be used by dog breeders. Objective: The researchers aim to find out if there genetic modifiers that could explain why some dogs with the mutation develop DM at 8 years of age while other 15 year-old dogs with the same mutation remain symptom free and if there are other mutations in the SOD1 gene or elsewhere that can cause DM or DM-like-diseases. The identification of modifier genes could prove particularly useful in breeds like the Boxer and Pembroke Welsh Corgi where the primary mutation is common, because it might provide an option fur selecting away from DM without disrupting breeding programs. Identification of additional genes will also give a better understanding of the disease and allow development of potential treatment strategies.
7. Mapping of Additional Genes Associated with Canine Degenerative Myelopathy
(Web Page; Fri Aug 16 12:36:00 CDT 2019)
Description: Background: Degenerative myelopathy (OM) is a fatal disease of the spinal cord causing progressive paralysis in mature dogs. In grant 821 these researchers performed genome-wide association mapping and identified an SOD gene mutation which is present in many breeds. A DNA test can now identify dogs at risk of developing DM, although many dogs that have the mutation never develop clinical symptoms. The availability of the DM test has raised questions that must be answered before the test can be used by dog breeders. Objective: The researchers aim to find out if there genetic modifiers that could explain why some dogs with the mutation develop DM at 8 years of age while other 15 year-old dogs with the same mutation remain symptom free and if there are other mutations in the SOD1 gene or elsewhere that can cause DM or DM-like-diseases. The identification of modifier genes could prove particularly useful in breeds like the Boxer and Pembroke Welsh Corgi where the primary mutation is common, because it might provide an option fur selecting away from DM without disrupting breeding programs. Identification of additional genes will also give a better understanding of the disease and allow development of potential treatment
8. Phenotypic Characterization of Peripheral Nerve Disease in Degenerative Myelopathy Dogs
(Web Page; Fri Aug 16 12:36:00 CDT 2019)
Description: Background: Degenerative myelopathy (DM) is a disease of the spinal cord causing progressive paraparesis. Though most commonly reported in German Shepherds, high disease prevalence also exists in other breeds, such as Cardigan and Pembroke Welsh Corgis (PWC), Rhodesian Ridgebacks, and Boxer dogs. Genome mapping and a candidate gene approach found a mutation in the canine SOD1 gene. Homozygosity for the mutant allele was associated with DM in five dog breeds which segregate for DM (Boxers, Pembroke Welsh Corgis, Rhodesian Ridgebacks, Chesapeake Bay Retrievers and German Shepherd dogs). Canine DM caused by SOD1 mutations resembles some forms of human ALS. Better characterization of the clinical disease spectrum in the DM affected dog, especially the nerve and muscle pathology will assist in establishing collaborations with ALS researchers and in development of therapeutic drug trials similar to those of human ALS. Objective: The researchers hypothesize that the nerve and muscle deterioration of canine DM will compare to that of human ALS. They are testing their hypothesis by performing clinical studies of the nerve and muscle and studying the pathology in DM affected dogs.
9. CANINE DEGENERATIVE MYELOPATHY: FROM GENE MUTATION DISCOVERY TO CLINICAL TRIALS
(Web Page; Tue Jan 25 13:21:00 CST 2022)
Description: Join us in this webinar for a better understanding of degenerative myelopathy.
(Web Page; Fri Aug 16 12:36:00 CDT 2019)
Description: Background: Degenerative myelopathy (DM) is a degenerative spinal cord disease affecting several breeds of dogs in adulthood. Affected dogs show gradual rear leg weakness and eventual complete loss of mobility. A particularly high prevalence in certain breeds, such as Boxer, Cardigan and Pembroke Welsh Corgis and Rhodesian Ridgebacks, suggests a genetic link. Objective: This study will first characterize DM in the Boxer to ensure that the disease is the same as has been identified in other breeds. Then, the researchers will identify the mutation responsible for DM and identify genes that contribute to the increased risk for DM in Boxers and other at-risk breeds of dogs. This mapping strategy will determine the location of DM mutation on the dog chromosome. They will then examine the genes at that chromosomal location to identify the DM mutation and develop a genetic test for predisposition to the disease. A DNA test will detect carriers of the mutation permitting wise breeding strategies to decrease the frequency of the disease in the breed. It will allow for definitive diagnosis of DM in affected dogs eliminating the need for expensive tests ruling out other conditions. The researchers expect this research to be applicable to several breeds presently affected by DM, and perhaps others in which the condition is not yet recognized.
Help Future Generations of Dogs
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.
