Identification of Bartonella henselae In Vivo Induced Antigens for Development of a Reliable Serodiagnostic Assay for Canine Bartonelloses

Bartonella, a genus of gram-negative bacteria, are associated with a wide spectrum of life- threatening diseases in animals and humans. More than 40 Bartonella species have been reported to infect mammalian reservoir hosts, and infection often leads to chronic bacteremia. At least ten Bartonella species have been implicated in association with serious diseases in dogs, including endocarditis, hemangiosarcoma, myocarditis, peliosis hepatis, polyarthritis and vasculitis. Despite biomedical advances and ongoing research in the field of canine bartonelloses, currently available PCR, culture, and serological based assays lack sensitivity for diagnosis of bartonelloses. Dogs throughout the United States and much of the world are exposed to Bartonella species.

From a public health perspective there is an increased risk of direct and vector-borne transmission of Bartonella species from animals to humans. These factors justify the need for the ongoing development of a reliable serodiagnostic modality and ultimately an effective vaccine for prevention of bartonelloses in dogs.

We will employ In-Vivo Induced Antigen Technology (IVIAT) to identify Bartonella in-vivo induced antigens, which will allow us to evaluate their potential as diagnostic markers for canine bartonelloses. This proposed study will result in development of a novel and sensitive ELISA assay for diagnosing Bartonella infection in dogs and will provide insights into the development of effective vaccine candidates for preventing Bartonella infection.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 2819


Edward Breitschwerdt, DVM ; North Carolina State University
Amount: $10,000

Strategic Prevention of Canine Hemangiosarcoma: Lifetime Follow-Up (Shine-On)

The Shine On project is designed to utilize complementary technologies to reduce the impact of hemangiosarcoma in companion dogs. This novel, potentially disruptive approach is the first of its kind where artificial intelligence applied to the results of a blood test will be used to assign dogs to a risk category for the development of hemangiosarcoma. The test, called the Shine On Suspicion (SOS) Test is designed to detect hemangiosarcoma at its earliest stages of development before it becomes a clinically-detectable disease. Dogs that are considered to be at high risk based on the SOS Test results will be eligible to receive the drug eBAT for strategic prevention; that is, to eliminate emergent hemangiosarcoma tumors before they form. eBAT is a rationally designed drug developed in the laboratory to attack the cells that initiate and maintain the cancer, as well as to make the environment inhospitable for their growth.

For the initial phase of the Shine On project, investigators developed and refined the SOS Test and the artificial intelligence methods to assign dogs to specific diagnostic categories and started to establish the utility of the test in early detection in a group of 209 presumably healthy, pedigreed Golden Retrievers, Boxers, and Portuguese Water Dogs, 6 years of age or older.

In this continuation phase of the Shine On project, this group of dogs that had the SOS Test will be followed for their lifetimes to identify any diagnosis of cancer or another chronic disease, the cause of death, and date of death. In addition, a subset of dogs determined to be at high risk using the SOS Test will receive eBAT in the setting of prevention and also followed over their lifetime to establish their outcomes. This project expects to develop firm proof of concept to support larger clinical trials, and eventual deployment of this approach to the veterinary community setting for all dogs at risk of developing hemangiosarcoma.

Co-sponsored through the collaborative efforts and generosity of the Golden Retriever Foundation and American Boxer Charitable Foundation, Grant Number: 02806-MOU


Jaime Modiano, VMD, PhD ; University of Minnesota
Grant Period: 8/1/2020 – 7/31/2024
Amount: $269,238

Pattern of Thyroid Function Tests during Recovery from Acute Nonthyroidal Illness

Hypothyroidism is the most common endocrine disease in dogs. A diagnosis of hypothyroidism relies on finding both appropriate clinical signs and low thyroid hormone levels. Unfortunately, other illnesses can suppress thyroid hormone levels and result in a misdiagnosis. This phenomenon of low thyroid hormone levels caused by a disease not involving the thyroid gland is known as nonthyroidal illness or euthyroid sick syndrome. It is important to distinguish between nonthyroidal illness and hypothyroidism as the treatment for each is different. Historically, the recommendation for a dog with nonthyroidal illness has been to resolve the underlying disease, followed by a recheck of thyroid hormone levels thereafter. However, the duration of time after resolution of the nonthyroidal illness necessary to perform accurate thyroid hormone level testing is unknown. This study will provide information about thyroid hormone levels during the course of nonthyroidal illness, and also establish the approximate duration of time for recovery of thyroid hormone levels to normal following illness resolution. These results will correlate clinically with more concrete recommendations for thyroid hormone level testing following resolution of nonthyroidal illness.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02643-A


Timothy Bolton, ; Virginia-Maryland Regional College of Veterinary Medicine
Amount: $5,000

Landmark Clinical Trial to Establish the Evidence-Based Use of Regenerative Medicine to Treat Tendon Injury in Dogs

This study will evaluate the effectiveness of Platelet-Rich Plasma (PRP) and stem cells in the treatment of the most common sporting injury in dogs: supraspinatus tendinopathy (similar to the rotator cuff injury in humans). Tendon injuries in dogs often progress undiagnosed and result in chronic lameness and pain. Ultimately, unassisted tendon healing results in scar formation and reduced function of the joint and surrounding muscle tissue. PRP and stem cell therapies aim to accelerate and promote healing through tissue regeneration and reduced scarring. The investigators will conduct a randomized, placebo-controlled clinical trial evaluating the effectiveness of PRP, adipose-derived, cultured stem cells (ASC) and commonly used stromal vascular fraction (SVF)cells to directly compare efficacy of intratendinous injection of ASC versus SVF, both of which are currently commercially available despite having limited scientific evidence of efficacy. The investigators hope to identify an effective treatment to supraspinatus tendon injury.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02107


Jennifer Barrett, DVM, PhD; Virginia-Maryland Regional College of Veterinary Medicine
Amount: $7,500

Examination of the Effects of Cannabidiol on Canine Neoplastic Cell Apoptosis/Autophagy and Potential for Chemotherapy Resistance or Sensitivity

Currently the use of cannabidiol (CBD) rich extracts for canine oncology patients is common, yet there is no data in canine oncology regarding the effects of CBD on canine cancer cells. Oncologists are wary of CBD use in their patients due to a lack of knowledge regarding the effects of CBD during chemotherapy.

Initial studies on cytotoxicity by the research team show that CBD has cytotoxic activity on a variety of canine cancer cell lines at modest concentrations in the laboratory. These effects cause apoptosis, or programmed cell death, within a very short time frame, suggesting a discrete mechanism.

The objective of this study is two-fold; 1) to determine if co-treatment of cancer cells with a common chemotherapeutic (doxorubicin) and CBD at varying concentrations affects chemotherapeutic cytotoxicity, and 2) to examine the molecular framework of the cell death response looking at the most commonly implicated pathways targeted in canine cancer treatment, including mechanisms of cell signaling and autophagy (removal of damaged cells).

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02643-A


Joesph J. Wakshlag, DVM, PhD; University of Florida
Amount: $2,500

Discovery of Novel Biomarkers of Canine Atopic Dermatitis through Lipid Profiling

Canine atopic dermatitis (CAD) is a common allergic skin disease of dogs with a strong genetic basis. CAD can severely affect the health and well-being of dogs and current diagnosis of CAD requires time-consuming and expensive procedures for the owner. Furthermore, the molecular mechanisms underlying this condition are not well understood.

Evidence from human studies suggests that several variants of atopic dermatitis (AD) exist with different mechanisms and responses to treatment. Therefore, new approaches to identify molecular markers that can help with better diagnosis and management are warranted. CAD and human AD are associated with changes in the composition of lipids in the epidermis which may precede the inflammation or result from the inflammation.

The investigators will analyze the lipid composition of the epidermis and blood of healthy dogs in comparison to dogs with CAD using a novel analytical method developed by their interdisciplinary team. The results of this work could lead to new, minimally-invasive tests for the diagnosis of CAD and for the prediction and monitoring of the response of CAD patients to treatment.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02651


Harm HogenEsch, DVM, PhD; Purdue University
Amount: $2,500

Embracing Polygenicity of Common Complex Disease in Dogs: Genome wide Association of Cruciate Ligament Rupture

Cruciate ligament rupture (CR) is a common disabling, degenerative condition of the knee. It places a large financial burden on the American public. Inflammation of the stifle and fraying of cruciate ligament fibers, particularly in the cranial cruciate ligament, eventually leads to ligament rupture with associated stifle instability in affected dogs. CR is a moderately heritable, complex disease with genetic and environmental risk.

CR is common in certain breeds, such as the Labrador Retriever, and rare in other breeds. There is a critical gap in knowledge regarding the genetic contribution to CR, as the number of genes influencing disease risk has never been studied in detail.

Our main goal is to comprehensively analyze the genetic features of the disease across the genome and use this knowledge to develop a genetic test for CR disease risk using genomic prediction. We aim to robustly estimate heritability, analyze the genetic architecture of CR, and advance genetic testing using genomic prediction in the Labrador Retriever, the most common purebred dog breed. The rationale for this work is that detailed knowledge of the genetic features of CR will advance development of a genetic test for CR risk using genomic prediction. This work will fundamentally advance knowledge of the genetic architecture of CR, a very common canine disease. Consequently, such knowledge will provide an invaluable guide to future research into other canine complex diseases. CR genetic testing would enable early identification of at-risk dogs for precision medical care, and selective breeding to reduce the disease burden.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02664


Peter Muir, BVSc, PhD; University of Wisconsin, Madison
Amount: $2,500

Targeted next generation sequencing panel for comprehensive testing of vector-borne pathogens

Diagnosing vector-borne disease (VBD) in dogs can be difficult for a number of reasons. First, there are many different disease-causing agents that can be transmitted from ticks/fleas, and the clinical signs caused by these agents in dogs can overlap. Additionally, because ticks/fleas can harbor more than one agent at a time, multiple pathogens may be passed to a dog with a single vector bite, resulting in co-infections.

VBD infections can initially present with non-specific signs, such as fever, lethargy, vomiting, diarrhea, and/or respiratory signs. Severe cases can be associated with neurologic signs. These signs can be a diagnostic conundrum. While initial blood work can be helpful and suggest VBD, it does not determine the infecting agent.

This study will develop a comprehensive next generation sequencing panel to detect and identify major VBD agents known to cause disease in dogs and to aid in diagnosis of active infections. Additionally, through parallel sequencing with this method, this panel will incorporate testing for additional infectious diseases that may cause GI, respiratory, or neurologic signs in dogs. The comprehensive nature of this sequencing panel should be a useful tool for surveillance of infectious diseases in the canine population for rapid identification of VBD in dogs and protection of pet owners from such zoonotic diseases.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02553


Rebecca Wilkes, DVM; Purdue University
Amount: $2,500 (May 2019) $7,500 (November 2019)

Clinical Trial for Evaluation of Propranolol and Doxorubicin in the Treatment of Canine Hemangiosarcoma

Canine hemangiosarcoma is a largely incurable cancer in dogs, and treatment approaches to improve outcomes have remained relatively stagnant over the past few decades. Treatment remains a challenge partly because the cancer is frequently detected at an advanced stage and because these tumors are often resistant to chemotherapies. Recently published reports showed that propranolol, a drug used to treat heart disease in humans and dogs, substantially increased the survival time of human angiosarcoma patients when used in combination with standard of care treatments. Propranolol was also shown to sensitize hemangiosarcoma cells to doxorubicin, providing a more effective way to kill tumor cells. Because angiosarcoma is strikingly similar to canine hemangiosarcoma, this multi-institutional clinical trial has been designed to determine the efficacy of propranolol in dogs with hemangiosarcoma when used in combination with surgery and chemotherapy.

The main goal of the study is to establish whether propranolol in combination with doxorubicin following surgery improves outcomes for dogs when compared to the use of chemotherapy and surgery alone. The investigators will also evaluate the plasma concentrations of propranolol achieved during dosing to assess whether the levels of propranolol correlate to survival times. If successful, the findings from this approach will be rapidly conveyed to the veterinary community, and the guidelines provided to clinicians for the use of propranolol and doxorubicin for the treatment of canine hemangiosarcoma.

Co-investigators: David R. Brown, PhD, University of Minnesota; Michael O. Childress, DVM, MS, Purdue University; Jennifer Mahoney, DVM and Pascale Salah, DVM, University of Pennsylvania

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02534


Erin Dickerson, PhD and Brian Husbands, DVM; University of Minnesota
Amount: $10,000

Investigation into Diet-Associated Dilated Cardiomyopathy in Dogs

Dilated cardiomyopathy (DCM) is a serious disease of the heart muscle whereby the heart becomes enlarged with weak contractions. DCM can result in  abnormal heart rhythms, congestive heart failure or sudden death. In dogs, DCM most often occurs in large- and giant-breeds, such as Doberman  Pinschers, Boxers, Irish Wolfhounds, and Great Danes; in these dogs, survival time after diagnosis is often only months, even with aggressive medical  therapy.

Recently, veterinary cardiologists have recognized DCM more frequently in all breeds of dogs including mixed breeds, and even those not  usually associated with DCM. There is suspicion that the disease in some dogs is associated with boutique, exotic ingredient, or grain-free (BEG) diets. Some affected dogs on such diets have shown reversal or improvement of their disease after changing their diet, supporting a potential association  between consumption of a BEG diet and development of DCM. A specific cause, however, has not been identified, despite extensive nutritional testing of  the dog foods and the canine patients. Moreover, the extent of the problem is unknown because only dogs that are symptomatic for DCM have been  reported. It is possible that more dogs may be affected but not yet showing signs of heart disease.

To investigate the extent of diet-associated heart  problems in dogs, this multi-institutional team of veterinary cardiologists and nutritionists will prospectively screen a large population of apparently  healthy dogs for DCM and compare important cardiac disease measures, including ultrasound of the heart, blood biomarker and taurine concentrations,  and the frequency of DCM in dogs eating BEG versus non-BEG diets.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02661


Darcy Adin, DVM; University of California, Davis
Amount: $5,000 (May 2019) $5,000 (November 2019)