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Research Update CHF 03137 MY2: Targeted Next Generation Sequencing Panel for Comprehensive Testing for Reproductive and Neurologic Pathogens of Dogs

Posted on by Crystal Smith in Research Update

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

Posted on by Crystal Smith in Research Update

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

Posted on by Crystal Smith in Research Update

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.

CHF-03045-A-EY-2-Oct24-Progress-Report-Summary

Research Update CHF 02661 Final: Investigation into Diet-Associated Dilated Cardiomyopathy in Dogs

Posted on by Crystal Smith in Research Update

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

Posted on by Crystal Smith in Research Update

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

Posted on by Crystal Smith in Research Update

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.

Continue reading “Research Update CHF 02403-MOU FINAL: Microphthalmia and Delayed Growth Syndrome in the Portuguese Water Dog” →

Research Update 02945-MOU EY3: Understanding the genetic basis of Addison’s disease in Portuguese Water Dogs

Posted on by Crystal Smith in Research Update

Over the first 3 years of this study, we have focused primarily on sample collection and running an initial set of genetics experiments. We collected samples mostly through PWD-related channels working directly with our collaborators in the PWDF/PWDCA. We also attended the PWD National Specialty in September 2021 and August 2022 to promote the study and collect samples, and we established a collaboration with Dr. Anita Oberbauer at UC Davis to share samples that she had already collected. To date, we have in hand 151 samples from affected PWDs and 319 samples from unaffected PWDs. Based upon relatedness, we have performed low-pass whole genome sequencing on 46 affected dogs and 55 unaffected dogs, and we have used data from these genotyping efforts to perform a genome-wide association study (GWAS). This initial study using traditional GWAS analysis approaches did not detect any major genetic differences between affected and unaffected PWDs. This is consistent with our thinking that the disease is genetically “complex.”

Continue reading “Research Update 02945-MOU EY3: Understanding the genetic basis of Addison’s disease in Portuguese Water Dogs” →

Research Update CHF 03055 MY2: Evaluating Reproductive Diseases in vitro with a 3D Canine Endometrial Organoid Model

Posted on by Crystal Smith in Research Update

Three-dimensional (3D) organoid cell cultures present new opportunities to improve understanding of common reproductive pathologies in the bitch in a laboratory setting rather than using live animals for research. This is an improvement on using research dogs by: i) addressing important welfare and ethical concerns, ii) allowing more controlled study of cellular responses due to different hormones and infectious agents, and iii) permitting high-throughput evaluation of treatments performed in tandem. This 3D reproductive organoid cell culture technology has not been attempted in canines prior to these studies. Continue reading “Research Update CHF 03055 MY2: Evaluating Reproductive Diseases in vitro with a 3D Canine Endometrial Organoid Model” →

Research Update End-year 9 CHF 01760-T: Use of Gene Therapy to Treat Dilated Cardiomyopathy

Posted on by Crystal Smith in Research Update

Dilated cardiomyopathy (DCM) is the second most common cause of heart disease in dogs, and medical management of the secondary signs is the only therapeutic option. The outcome for affected dogs depends on the stage of disease and the breed. Once diagnosed, dogs typically exhibit rapid and uniform progression to congestive heart failure (CHF), with most living less than 6 months.

Continue reading “Research Update End-year 9 CHF 01760-T: Use of Gene Therapy to Treat Dilated Cardiomyopathy” →

Research Update CHF 03169 MY1: Characterization of hookworm resistance in dogs with a novel diagnostic test for early intervention

Posted on by Janet Boyd in Research Update

The dog hookworm, Ancylostoma caninum, is the most common worm parasite of dogs in the United States. It is specific to dogs but can infect humans by entering through intact skin (zoonotic), causing cutaneous larval migrans, a painful skin condition. Treatment options in dogs include the benzimidazole (BZ) drugs. However, hookworms have recently developed resistance to BZs. This resistance has been associated with two mutations – F167Y and Q134H in a gene of the worm. We have developed a PCR to test for these two mutations in the feces of infected dogs. The PCR test tells us if the mutations causing resistance is present in the sample or not, and also at what level the mutation is present. We have currently tested the PCR on the feces of 75 dogs from the mid-western United States. Continue reading “Research Update CHF 03169 MY1: Characterization of hookworm resistance in dogs with a novel diagnostic test for early intervention” →