The study has been open for enrollment since Jan 1, 2025. Thus far, no dogs have been enrolled, so there is no clinical or objective data to report.
Research Update 02945-MOU FINAL: Understanding the genetic basis of Addison’s disease in Portuguese Water Dogs
Over the course of this study, we collected DNA samples from hundreds of affected and unaffected PWDs. We performed high-coverage whole-genome sequencing of 16 PWDs (and used publicly available resources to acquire an additional 20 high-coverage samples); low-pass whole-genome sequencing of 101 PWDs, and class II MHC genotyping of the same 101 PWDs. We focused our principal analyses on the 101 low-pass/MHC PWDs because these dogs formed the least-related population out of the hundreds of DNA samples collected.
One of the main goals of this study was to perform a genome-wide association study to look for regions of the genome associated with Addison’s disease in the breed. We performed this GWAS using a variety of approaches with the imputed low-pass data, but unfortunately, we were unable to find a genomic region significantly associated with Addison’s disease. This implies that within PWDs, Addison’s may be: (1) fixed, meaning all PWDs are equally predisposed; (2) highly polygenic, meaning that many genomic regions are responsible for Addison’s disease, however our study did not have enough samples to identify these multiple regions; (3) caused by mutations that are not easily detectable by the methods we used, such as structural genomic variants; (4) caused by a combination of these factors. Continue reading “Research Update 02945-MOU FINAL: Understanding the genetic basis of Addison’s disease in Portuguese Water Dogs”
Research Update CHF 03137 FINAL: Targeted Next Generation Sequencing Panel for Comprehensive Testing for Reproductive and Neurologic Pathogens of Dogs
Study Overview:
In this study, we aimed to develop a comprehensive targeted next-generation sequencing (tNGS) panel to identify common infectious agents related to neurologic and reproductive disease in dogs, while also incorporating less common zoonotic agents that can spread to humans into a single test. This type of test would allow for the identification of a broader range of infectious agents than the routine tests that are normally performed.
How We Did It:
We developed two pools of primers (short DNA sequences) to detect 34 different infectious agents associated with neurologic/reproductive disease in dogs. We combined the amplification of the agents provided by the use of these primers together with a sequencing assay to both detect, and where possible, characterize the infectious agents if present in the dog’s sample. Continue reading “Research Update CHF 03137 FINAL: Targeted Next Generation Sequencing Panel for Comprehensive Testing for Reproductive and Neurologic Pathogens of Dogs”
Research Update CHF 03194 EY1: A Blueprint to Develop Next-Generation CAR T Therapy for Canine Lymphoma
High grade B cell lymphoma is a cancer frequently diagnosed in older dogs, with Golden Retrievers and Bernese Mountain Dogs being particularly predisposed. Standard veterinary care involves chemotherapy and whilst patients initially respond well, the disease proves to be fatal for most dogs diagnosed. In human medicine, chimeric antigen receptor (CAR) T cell therapy, in which the patient’s T lymphocytes are engineered to target and kill their cancer, has been remarkably successful for treating B cell lymphoma. Continue reading “Research Update CHF 03194 EY1: A Blueprint to Develop Next-Generation CAR T Therapy for Canine Lymphoma”
Research Update CHF 03137 MY2: Targeted Next Generation Sequencing Panel for Comprehensive Testing for Reproductive and Neurologic Pathogens of Dogs
The goal of this project is to validate respiratory and neurologic disease testing using a targeted nextgeneration sequencing (tNGS) panel we previously developed. We expect this assay, which includes 34 different pathogens known to be associated with reproductive/neurologic disease in dogs, will perform as well as individual real-time PCR assays designed to detect each of these pathogens individually. This type of comprehensive testing takes the guesswork out of choosing which individual tests or small panel of tests to run to diagnose disease.
We have now completed testing 100% of the pathogens/DNA representing the pathogens that are detectable with this assay, and all but 1 could be detected. The pathogen missed was Campylobacter jejuni. This one was included for its possible role in reproductive disease, but it is more likely to cause diarrhea in dogs. Therefore, we will not redesign the assay at this point. Continue reading “Research Update CHF 03137 MY2: Targeted Next Generation Sequencing Panel for Comprehensive Testing for Reproductive and Neurologic Pathogens of Dogs”
Research Update CHF 02534 EY5 Update: Clinical Trial for Evaluation of Propranolol and Doxorubicin in the Treatment of Canine Hemangiosarcoma
We have completed enrollment for the trial. We are currently analyzing the pharmacokinetic data obtained from the blood samples of dogs enrolled in the study. The project goals have not been modified. Our overall objective is to determine a clinically optimal dose and estimate the efficacy of propranolol in dogs with hemangiosarcoma when given as an adjunct to chemotherapy. Specifically: Objective 1: We will confirm the tolerability and estimate the clinical benefit of propranolol in combination with doxorubicin. Continue reading “Research Update CHF 02534 EY5 Update: Clinical Trial for Evaluation of Propranolol and Doxorubicin in the Treatment of Canine Hemangiosarcoma”
Research Update CHF 03045-A EY2 Oct-24: Artificial Intelligence and Machine Learning for Diagnosis of Dog Sperm Morphology
Semen samples from 62 dogs have been used to build an image database containing 11,464 images of a single sperm obtained using phase-contrast under 1000X magnification. Three specialists are currently classifying the images and building an annotated database to be used to train and test an optimized algorithm for sperm morphology classification. Considerable progress was made on the development of a neural network for sperm evaluation. Two methods to standardize image size proved satisfactory, with image stretching resulting in better accuracy when compared to use of black borders.
Additional possibilities for improving the performance of the implemented model will be investigated, including adjusting training hyperparameters, performing preprocessing alternatives such as contour detection before feeding the neural network, and optimizing the neural network architecture itself. Other techniques, such as regularization, insertion of normalization layers, and dropout, are also suggested to achieve better results.
The Principal Investigator requested and was awarded a no-cost extension to 12/31/2024.
Research Update CHF 02661 Final: Investigation into Diet-Associated Dilated Cardiomyopathy in Dogs
The study titled “Investigation into Subclinical Diet-Associated Dilated Cardiomyopathy in Four Dog Breeds” has resulted in 4 peer-reviewed manuscripts published in the Journal of Veterinary Internal Medicine, the American Journal of Veterinary Research and Scientific Reports.
The results of this work demonstrated higher levels of cardiac troponin I in dogs eating grain-free (GF) dog foods or foods that have peas, lentils or potatoes in the top 10 ingredients compared to dogs eating grain-inclusive (GI) dog foods or foods without peas, lentils, or potatoes in the top 10 ingredients. Cardiac troponin I is a blood marker that indicates injury to the heart muscle and therefore this study provides information on how heart disease occurs in some dogs eating GF diets. Additionally, we showed that cardiac troponin I decreased, and an echocardiographic (ultrasound of the heart) measure of contractility improved in dogs fed GF diets that were changed to a GI diet without peas or lentils 1 year after this diet change. This is important information because it shows that apparently healthy dogs can have subtle heart muscle injury that can improve with diet change. Therefore, this data is supportive of causation. Continue reading “Research Update CHF 02661 Final: Investigation into Diet-Associated Dilated Cardiomyopathy in Dogs”
Research Update CHF 02806-MOU EY4: Strategic Prevention of Canine Hemangiosarcoma: Lifetime Follow-Up
The goal for this project is to develop a reliable, accessible, and actionable test to identify dogs at risk for hemangiosarcoma during the earliest stages of disease and to use a strategic, rationally designed approach to prevent its occurrence in these high-risk dogs before it becomes clinically detrimental and life-threatening. The study has two objectives. The first is to determine the most reasonable duration of an SOS test result. In other words, how long can a low-risk SOS test result be trusted and how much time might elapse between a high-risk SOS test result and the development of hemangiosarcoma. The second aim is to continue periodic testing for dogs previously enrolled in the Shine On study whose test result would have placed them in a high-risk category for development of hemangiosarcoma, and to provide eBAT as a strategy for prevention in up to 12 of these dogs. Continue reading “Research Update CHF 02806-MOU EY4: Strategic Prevention of Canine Hemangiosarcoma: Lifetime Follow-Up”
Research Update CHF 02403-MOU FINAL: Microphthalmia and Delayed Growth Syndrome in the Portuguese Water Dog
Through the generosity of the AKC-CHF and the PWD breeders, we have been able to find the genetic defect that causes puppy eye syndrome (microphthalmia syndrome) in the Portuguese Water Dog. The defect consists of a large insertion and deletion within a gene that is responsible for ocular development and bone marrow regulation.