Research Update 03368-MY1: Advancing Canine Health: Liquid Biopsy for Early Relapse Detection and Improved Treatment of Mast Cell Tumors

Mast cell tumor (MCT) is the most common malignant canine skin tumor, which accounts for 16~21% of all skin tumors. Although all breeds have a potential risk for developing MCTs, many pure breeds(e.g., Boxers, Boston Terriers) are predisposed, resulting in a high disease incidence. Despite the efforts, clinical management decisions are difficult because of the challenging biological behavior of some MCTs and the inaccuracy of the predictive and prognostic biomarkers or other molecular descriptors (i.e., c-KIT staining pattern and mutation status, KI-67, AgNOr). While surgery is the mainstay of managing canine MCTs, toceranib phosphate (Palladia) showed clinical benefits to those MCTs that require chemotherapy. However, most will develop acquired resistance within months of starting the treatment.

Currently, there are no means of identification of treatment resistance apart from clinical characteristics, which usually capture the relapse late, when the disease is already disseminated. In addition, most procedures used for monitoring patients with MCT require sedation or general anesthesia. Early disease progression detection by quantifying minimal residual disease is thus an unmet clinical need. The development of such an assay could significantly affect disease management, improve patient outcomes and welfare, and help emerge novel therapeutic targets through better patient stratification. Continue reading “Research Update 03368-MY1: Advancing Canine Health: Liquid Biopsy for Early Relapse Detection and Improved Treatment of Mast Cell Tumors”

Research Update MAF D24CA-535: Studying Hemangiosarcoma Subtypes and Treatment Response

SUMMARY: Researchers are studying if hemangiosarcoma (HSA) subtypes influence how affected dogs respond to treatment – a step toward precision medicine for these patients.

THE PROBLEM: Hemangiosarcoma is a serious and usually fatal cancer of dogs. Most dogs die of the disease by  within 4-6 months post-diagnosis, even with aggressive treatment. However, some research suggests that hemangiosarcoma is not one disease but comprised of different subtypes, and these subtypes might be related to  longevity and response to therapy.

THE PROJECT: This research team has previously found that dogs with one type of HSA are more likely to live longer than dogs that have a different type of HSA. This may explain why current treatments fail to help most dogs with HSA live longer despite aggressive care. To take a closer look at this finding, researchers will identify the HSA type or signature in tumors from dogs that have lived longer than other dog patients with HSA. The team is using data from a study in progress to inform their evaluation of archived tissues to assess prevalence and survival. Continue reading “Research Update MAF D24CA-535: Studying Hemangiosarcoma Subtypes and Treatment Response”

Research Update CHF 02806-MOU FINAL: 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.

To complete the first objective, we conducted surveys to determine the health status of every dog enrolled in Shine On phase-3 (SO3, the early detection phase) at 6-month intervals. Continue reading “Research Update CHF 02806-MOU FINAL: Strategic Prevention of Canine Hemangiosarcoma: Lifetime Follow-Up”

Research Update CHF 03243-A EY1: Comparison of Clorazepate and Levetiracetam as Pulse Therapy for the In-Home Management of Cluster Seizures in Dogs with Idiopathic Epilepsy: A Pilot Study

Idiopathic epilepsy is the most common chronic neurological disorder of dogs. Approximately half of dogs with idiopathic epilepsy have cluster seizures, defined as 2 or more seizures within a 24-hour period, and have an increased risk of epilepsy-related complications or death associated with this seizure pattern. Treatment regimens that include in-home administration of emergency medication for cluster seizures are commonly prescribed, but there is a lack of evidence on which to base treatment recommendations. Continue reading “Research Update CHF 03243-A EY1: Comparison of Clorazepate and Levetiracetam as Pulse Therapy for the In-Home Management of Cluster Seizures in Dogs with Idiopathic Epilepsy: A Pilot Study”

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”