Displaying results 11 - 20 of 76 items found.
(Web Page; Tue Aug 24 09:26:00 CDT 2021)
Description:
Degenerative myelopathy (DM) is an adult onset disease of the spinal cord causing progressive weakness and paralysis of the hind limbs and eventually all limbs. Mutations in an enzyme that converts superoxide to water and hydrogen peroxide, superoxide dismutase 1 (SOD1), have been linked to DM and amyotrophic lateral sclerosis (ALS-Lou Gehrig's disease). DM is associated with degenerative loss of axons, which transmit signals from the brain and spinal cord to their targets (muscle). Currently no diagnostic test exists that would allow for repeated measurements with minimal invasiveness. Dr. Coates proposes developing a test that would assay the blood and cerebrospinal fluid (CSF) for proteins that are exclusively found in axons under non-disease conditions, referred to as neurofilament proteins. The investigators will correlate the concentrations of neurofilament proteins in CSF and blood with disease stage and anticipate that neurofilament protein concentration in blood and CSF will increase as disease progresses. Such a test will allow for minimally invasive monitoring of disease. Furthermore, such a diagnostic test could be used to measure the success of therapy, which may be underway in a cohort of DM-affected dogs [Boxers and Pembroke Welsh Corgis (PWC)] (funded by NIH/NINDS). This work will complement the test for neurofilament proteins with other studies that measure disease progression such as specific MRI techniques to evaluate the brain and spinal cord and electrical testing of the muscle and nerves. These are functional disease markers that are also being studied in ALS patients.
Funding for the research is provided through the efforts and generosity of the American Boxer Charitable Foundation. The AKC Canine Health Foundation supports the funding of this effort and will oversee grant administration and scientific progress.
12. Genetic Test for Degenerative Myelopathy
(Web Page; Sun Dec 05 20:59:00 CST 2010)
Description: Article describes the genetic test available for degenerative myelopathy in the Boxers, Pembroke Welsh Corgis, Chesapeake Bay Retrievers and Rhodesian Ridgebacks.
(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 in adult dogs. 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 identified 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 outcome assessment measures and understanding of the spinal cord 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 spinal cord dysfunction and nerve root deterioration of canine DM will compare to that of human ALS. They are testing their hypothesis by performing clinical studies of gait and studies of spinal cord and nerve root tissues in DM affected dogs.
14. Exploring New Tools for Degenerative Myelopathy Diagnosis
(Web Page; Mon Nov 08 09:36:00 CST 2021)
Description: Investigators at the University of Missouri explored ways to diagnose and monitor the progression of degenerative myelopathy that are repeatable and less invasive than current diagnostic tests.
15. Gene Therapy for Canine Degenerative Myelopathy
(Web Page; Thu Oct 17 14:34:00 CDT 2019)
Description:
Degenerative myelopathy (DM) is a devastating neurodegenerative disease that affects multiple breeds of dog. DM is an adult-onset disease that manifests at the later stages of life. It is characterized by progressive weakness and inability to control hindlimbs, ultimately leading to involvement of forelimbs and complete paralysis. With no current treatments available, euthanasia is the only option available for DM-affected dogs. Recent studies have identified mutation in the Superoxide dismutase 1 (SOD1) gene to be a high risk factor associated with canine DM. In humans, mutations in the same SOD1 gene cause Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disorder very similar to canine DM. It is also shown that reduction of mutant SOD1 in ALS mouse models provides beneficial effects. Hence, therapeutic approaches to reduce the expression of mutant SOD1 in DM-affected dogs may improve survival and preserve neurologic function. In this study, a viral-based gene therapy approach to treat DM will be evaluated, utilizing Adeno-associated Virus 9 (AAV9) mediated delivery of shRNA to reduce the mutant SOD1 in DM affected dogs. AAV9 is a safe, well tolerated and widely used vector for gene therapy in animals as well as for humans. If successful, this one-time treatment with AAV9 SOD1 shRNA will result in improved quality of life, and significantly extend the survival of dogs affected with this previously hopeless disease.
16. Riluzole as a Neuroprotectant in Canine Degenerative Myelopathy
(Web Page; Mon Apr 22 08:22:00 CDT 2024)
Description:
Degenerative myelopathy (DM) is an adult-onset spinal cord disease in dogs that causes progressive weakness and paralysis of the hind limbs and eventually all limbs. We now understand that DM is similar to some forms of amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) in humans. To date, there is no treatment to slow the clinical progression of DM. A hallmark of the disease is loss of a transporter that takes up glutamate in central nervous system tissues. Glutamate is an excitatory neurotransmitter that serves as a chemical messenger between nerve cells. Excess levels of glutamate will cause neuron death. The focus of this study is the evaluation of a drug, riluzole, that will counteract the buildup of glutamate. This FDA approved drug has been shown to extend survival in ALS patients. The long-term goal is to establish effective clinical strategies for treatment of canine DM through the efficient conduct of veterinary clinical trials. Toward this goal, the research team 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 to evaluate novel therapies and disease measures in a standardized way across multiple institutions. Investigators 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. This hypothesis will be tested 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, a structural protein found in neurons, is a valuable biological marker to assess the clinical progression of DM in dogs.
To participate in this study, learn more here.
17. Research Spotlight: Degenerative Myelopathy
(File; Fri Mar 17 08:48:00 CDT 2017)
Description: Learn how your investment is making a difference in the study of Degenerative Myelopathy.
(Web Page; Thu May 25 09:53:00 CDT 2023)
Description: CHF announces funding for a groundbreaking study evaluating a potential treatment for canine degenerative myelopathy.
(Web Page; Tue Apr 14 13:42:00 CDT 2020)
Description: A brief summary of the Canine Health Bytes webinar on canine degenerative myelopathy, presented by Dr. Joan Coates in October 2019.
20. Identification of Genetic Risk Factors in Degenerative Myelopathy in German Shepherd Dogs
(Web Page; Sun Mar 05 08:36:00 CST 2023)
Description:
Canine degenerative myelopathy (DM) is a naturally occurring progressive adult-onset neurodegenerative disease that is fatal. Performing genome-wide association studies (GWAS) in Pembroke Welsh Corgis (PWC), investigators identified an association to a SOD1 variant, coding for the E40K amino acid substitution, that occurs in >180 dog breeds. The vast majority of breeds with DM have the same SOD1 mutation. Using PWC with the SOD1 disease allele, comparisons were made between early onset cases and elderly healthy dogs that also were homozygous for the DM risk allele. A mutation in SP110 was found to predispose to early onset DM. Given that the frequency of the SOD1 mutation and disease is variable within and across breeds investigators believe that multiple additional genes may affect at what age the disease starts. Overall, the research team has collected DNA from 20,000 German Shepherd Dogs (GSD) and genotyped them for the standard SOD1 mutation to demonstrate the disease is frequent and the allele frequency is 35% for this breed. This study will perform health updates for already collected and novel GSDs and look at the age of onset distribution for DM. As with the PWC studies, comparisons will be made between old healthy GSDs and GSDs with the earliest onset of DM (both categories having two copies of the SOD1 mutation). This should identify novel modifier genes determining if SOD1+ dogs get the disease early or late (or not at all). Finally, whole-genome sequencing of three GSDs with the disease, but lacking the known SOD1 mutation, will help identify additional risk factors. Together, these aims may develop more accurate genetic tests for DM in GSDs and other breeds.
Funding for the research is provided through the collaborative efforts and generosity of the German Shepherd Dog Club of America. The AKC Canine Health Foundation supports the funding of this effort and will oversee grant administration and scientific progress.
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