Research Updates from the 2019 AKC Canine Health Foundation National Parent Club Canine Health Conference

The AKC Canine Health Foundation (CHF), a non-profit organization dedicated to advancing the health of all dogs and their owners, hosted the 2019 National Parent Club Canine Health Conference in St. Louis, MO on August 9 – 11, 2019. The biennial event, sponsored by Purina, brought together researchers, American Kennel Club (AKC) Parent Club members, breeders, veterinarians, theriogenology residents, and veterinary students to discuss the latest findings in canine health research. This year’s conference included lectures on Nutrition & Disease, Autoimmune Disease, Infectious Disease & Cancer, and Genetics & Genetic Testing. There were also panel discussions with researchers, social events to facilitate networking and collaboration among attendees, and break-out sessions for veterinary students whose attendance was sponsored by the Orthopedic Foundation for Animals (OFA) and the AKC, all with the goal of improving the health and well-being of dogs.

Note - registrants may fall into more than one category.

As the largest funder in the world of health research exclusively for dogs, CHF currently manages an active research grants portfolio of almost $10 million in 128 research studies addressing canine cancer, infectious diseases, cardiology, epilepsy and much more, available to view at www.akcchf.org/portfolio. Since the organization was founded in 1995, more than $52 million in canine health research and educational grants have been awarded, and CHF-supported research has resulted in over 750 peer-reviewed scientific publications cited more than 26,000 times, demonstrating the impact and relevance of their funded studies. Highlights of CHF-funded research findings presented at the 2019 conference are listed below.

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Nutrition & Disease

New Approaches to Diagnosis and Therapy of Intestinal Microbiota Dysbiosis

Jan S. Suchodolski, DrMedVet, PhD, DACVM, AGAF; Texas A&M University

Genetic testing has illuminated just how many microbes live with us. Our understanding and appreciation of the complex ecosystem comprised of ourselves and these microbes continues to grow. Fecal dysbiosis in dogs can now be diagnosed with PCR and is often associated with diseases such as exocrine pancreatic insufficiency, chronic enteropathy, and antibiotic-induced enteropathy. Dr. Suchodolski’s research is exploring the metabolic consequences of gastro-intestinal inflammation and dysbiosis in dogs. He cautions veterinarians that antibiotics will always affect the patient’s fecal microbiome, which may not fully recover after such treatment. He is using fecal microbiota transplants (given via enema) with varied success in dogs.

Effects of Probiotics on the GI Microbiome and Immune System of Dogs and Cats

Michael Lappin, DVM, PhD, DACVIM (Small Animal Internal Medicine); Colorado State University

Dr. Lappin advocates for evidence-based medicine when choosing and using a probiotic in veterinary medicine. Peer-reviewed literature shows that probiotics do have a positive effect in dogs, such as:

• speeding the return of the intestinal microbiota to normal after insult
• increasing IgA levels in feces and therefore boosting intestinal mucosal defenses, and
• stimulating the immune system to speed the recovery of clinical demodex.

The Gut-Brain Axis and Those “Gut Feelings”: Impact of BL999 (Bifidobacterium longum) on Anxious Dogs

Ragen T.S. McGowan, PhD; Purina

Purina® ProPlan® Veterinary Supplements Calming Care was released in January 2019 after research showed that dogs receiving the probiotic strain BL999 showed a decrease in anxious behaviors such as barking, jumping, and spinning; increased exploratory behavior in a novel environment; and reduced salivary cortisol concentrations and heart rate.

Food for Thought: Updates on Nutritional Considerations and Heart Disease Staging in Dogs

Darcy Adin, DVM, DACVIM (Cardiology); University of Florida

Dr. Adin is researching refractory congestive heart failure in dogs – defined as persistent pulmonary congestion despite the use of adequate and escalating diuretic doses. Preliminary results show:

• Blood concentrations of furosemide do not correlate well with oral dosage, especially at high dosages in dogs with advanced heart disease. The underlying mechanism of this discrepancy – such as poor absorption, administration on a full or empty stomach, or unpredictable bioavailability – requires further research.
• Serum chloride is lower in dogs with refractory congestive heart failure compared to those with controlled disease. Hypochloridemia in humans appears to be not only associated with advanced heart failure, but may also drives diuretic resistance, so the same may be true in dogs.
• Some dogs with refractory congestive heart failure had evidence of greater renin-angiotensin aldosterone system (RAAS) inhibition than dogs with controlled congestive heart failure. Additional study is needed to identify the cause of this altered and favorable renin-angiotensin-aldosterone profile.  These findings suggest that RAAS inhibition was adequate in these dogs receiving recommended dosages of ACE-inhibitors and spironolactone and that RAAS overactivation was not necessarily the cause of refractory congestive heart failure.  Therefore, stronger, more consistent diuresis with the more potent diuretic, torsemide, may be considered a reasonable approach to addressing refractory heart failure, especially in light of the findings of poor furosemide bioavailability. 

CURRENT CHF GRANTS
• 02661: Investigation into Diet-Associated Dilated Cardiomyopathy in Dogs
• 02436: Predicting Disease Stage and Diuretic Responsiveness in Dogs with Acquired Heart Disease

An Update on Cannabidiol Research in Dogs

Stephanie McGrath, DVM, MS, DACVIM (Neurology); Colorado State University

Dr. McGrath is the principal investigator for a CHF-funded clinical trial evaluating the efficacy of CBD oil to treat drug-resistant canine epilepsy. The trial has reached almost two-thirds of their enrollment goal and is ongoing; no results are available in this double-blinded, placebo-controlled research.

Dr. McGrath provided the following tips for sourcing CBD oil:

• The manufacturer should provide a certificate of analysis (ideally performed by a 3rd party) and sponsor research on their products.
• The product should have high CBD and low THC (less than 0.3%) levels.
• It is still a buyer beware market, but ask the company – make them prove their work!

CURRENT CHF GRANTS
• 02323: Efficacy of Cannabidiol (CBD) for the Treatment of Canine Epilepsy

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Autoimmune Disease

Addison's Disease: A Research Update

Steven Friedenberg, DVM, PhD, DACVECC; University of Minnesota

As a criticalist and geneticist, Dr. Friedenberg is studying the genetic and immunologic mechanisms underlying canine Addison’s Disease (AD). His team has identified a single nucleotide polymorphism (SNP) associated with 25% of AD cases in standard poodles less than two years of age. They have also identified an autoantibody that is expressed within 30 days of AD diagnosis. Additional research is underway to use these discoveries in the prediction, prevention, and treatment of this challenging disease.

CURRENT CHF GRANTS
• 02428: Identifying the Disease-Defining Autoantibodies in Canine Addison's Disease
• 02348: Whole Blood Transcriptome Profiling of Dogs with Immune-Mediated Hemolytic Anemia (IMHA)
• 02531 (Co-investigator): Identification of Genetic Risk Allele(s) Associated with the Development of Tricuspid Valve Dysplasia in the Labrador Retriever

Clinical Characteristics of Steroid Responsive Meningitis-Arteritis in Dogs in North America

Karen Muñana, DVM, MS, DACVIM (Neurology); North Carolina State University

The disease once known as “Beagle Pain Syndrome” is now recognized in other breeds and known as Steroid Responsive Meningitis-Arteritis. Results of a CHF-funded study on this disease were recently published (Lau J, Nettifee JA, Early PJ, Mariani CL, Olby NJ, Muñana KR. Clinical characteristics, breed differences, and quality of life in North American dogs with acute steroid-responsive meningitis-arteritis. J Vet Intern Med. 2019;1–9. https://doi.org/10.1111/jvim.15543) and presented at the conference. Clinicians should note:

• Golden Retrievers and Wirehaired Pointing Griffons should be added to the list of breeds commonly affected by this disease.
• The disease responds well to treatment with prednisone, but relapses are common and the side effects of steroid use have a significant impact on quality of life for the dog and owner.

Learn more from the RACE-approved webinar “Understanding Steroid Responsive Meningitis-Arteritis and Other Inflammatory Neurological Disorders in Dogs” available at www.akcchf.org/vetvine.

CURRENT CHF GRANT – 02561: Is Gut Dysbiosis Associated with Canine Idiopathic Epilepsy?
RECENT CHF SRMA GRANT – 2017 Clinician-Scientist Fellowship – North Carolina State University

A Case of Mistaken Identity: Autoimmunity & Endocrine Disorders

Anita Oberbauer, PhD; University of California, Davis

The keynote address was given by the 2019 AKC Canine Health Foundation Asa Mays, DVM Awardee for Excellence in Canine Health Research, Dr. Anita Oberbauer. She reviewed the pathophysiology of autoimmunity as it relates to endocrine disease, including research on genetic variants within the dog leukocyte antigen (DLA) genes. DLA is the canine version of the human major histocompatibility complex (MHC). The takeaway message was that genetic variability in DLA genes confers greater resistance to disease, but low DLA variability does not necessarily reduce immunocompetence. We have a lot more to learn about the immune system!

CURRENT CHF GRANT – 02488: Addison's Disease and Symmetrical Lupoid Onychodystrophy in Bearded Collies Provide Common Ground for Identifying Susceptibility Loci Underlying Canine Autoimmune Disorders

Vector-borne Infections and Autoimmune Disease: What's the Link?

Linda Kidd, DVM, PhD, DACVIM (Small Animal Internal Medicine); Western University of Health Sciences

Vector-borne and immune-mediated diseases often present with the same non-specific symptoms and varied seasonal prevalence. Clinicians should consider the geography, signalment, occupation, and minimum database results of any patient with suspected immune-mediated disease in order to conduct the appropriate testing for underlying vector-borne disease. Since antibody and antigen levels differ between the acute and chronic stages of infection, it is important to perform repeated serologic and PCR testing to diagnose infection.

Results of this research are available in the RACE-approved webinar “Immune-Mediated Hemolytic Anemia (IMHA): Underlying Disease Screening in Dogs. What Should I Be Looking For?” at www.akcchf.org/vetvine.

RECENTLY COMPLETED CHF GRANT – 02285-A: Thrombocytopenia and Occult Vector-Borne Disease in Greyhound Dogs: Implications for Clinical Cases and Blood Donors

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Infectious Disease & Cancer

Emergence of Canine Leptospirosis: Coming Soon to a Puddle Near You?

Jason Stull, VMD, MPVM, PhD, DACVPM; Ohio State University and University of Prince Edward Island

Dr. Stull presented findings from his CHF-funded epidemiologic research on canine leptospirosis. After reviewing leptospirosis test results (data provided by IDEXX Laboratories, Inc.) in the United States and Canada during eight- and ten-year periods respectively, as well as conducting a case-controlled study of leptospirosis in the Chicago, IL area, Dr. Stull shared the following findings and recommendations:

• Young dogs (less than 5 years old) have a higher risk for leptospirosis than older dogs and cases do occur in dogs less than six months old.
• Seasonal variation in test positive prevalence varies with geographical region.
• The case-control study showed that small dogs (less than 14 lb) were more likely to be affected than larger dogs (33-60 lb) and that dogs not vaccinated for leptospirosis were more likely to be affected than dogs that had received appropriate leptospirosis vaccination protocol.
• Clinicians should be aware that leptospirosis can be found in small, young, and urban dogs.

CURRENT CHF GRANTS
• 02284-A: Lyme Disease in Dogs: Prevalence, Clinical Illness, and Prognosis
• 02380-A: Estimating Prevalence and Identifying Risk Factors for Canine Leptospirosis in North America
• 02532-A: Canine Influenza: Occurrence, Spatial and Temporal Trends and Identifying Modifiable Factors to Reduce Transmission at Events in the United States

 

The genus Bartonella and Vasoproliferative Cancers in Dogs and Humans

Edward B. Breitschwerdt, DVM, DACVIM (Small Animal Internal Medicine); North Carolina State University

Bacteria can produce chronic inflammation, cell proliferation, hormonal alterations, and toxic metabolites and are major contributors to the incidence of cancer worldwide. Organisms within the genus Bartonella specifically target multiple cell types to alter cell proliferation and survival, stimulate inflammation, and stimulate production of vascular endothelial growth factor. The Vector Borne Diseases Diagnostic Laboratory team at North Carolina State University has identified Bartonella DNA in the tumor and non-tumor tissues of 74% of dogs with hemangiosarcoma. This means that seven out of ten dogs in the United States with hemangiosarcoma have Bartonella DNA in their tissues (regardless of the primary tumor location). Additional study is needed to leverage this robust association between Bartonella infection and canine hemangiosarcoma to improve diagnostic, treatment, and prevention strategies for this deadly cancer.

CURRENT CHF GRANTS
• 02287: Enhanced Testing for the Diagnosis of Bartonellosis in Dogs
• 02519: Prevalence of Bartonella spp. Infection in Dogs with Cardiac and Splenic Hemangiosarcomas Within and Between Geographic Locations
• 02550: The Role of Bartonella spp. Exposure and Cardiac Genetic Variation on the Clinical Expression of Arrhythmogenic Right Ventricular Cardiomyopathy in the Boxer Dog

 

Advances in Cancer Immunotherapy

Steven Dow, DVM, PhD, DACVIM (Small Animal Internal Medicine); Colorado State University

A multi-modal approach utilizing surgery, radiation, chemotherapy, and immunotherapy is essential for canine cancer treatment. Rapid advances are underway in the field of canine cancer immunotherapy and include:

• Several early phase clinical trials evaluating monoclonal antibodies that target checkpoint molecules (molecules that regulate T cell function)
• Study of tumor microenvironment modifiers that alter the microenvironment and make it less hospitable to cancer. One example is a clinical trial combining losartan and toceranib (Palladia®) to treat canine osteosarcoma. Both osteosarcoma and hemangiosarcoma have monocyte-rich microenvironments, but losartan blocks canine monocyte migration and may therefore be a useful treatment tool.

CURRENT CHF GRANT – 02487: OX40 Checkpoint Molecule Targeted Antibodies for Cancer Immunotherapy in Dogs

Propranolol and Hemangiosarcoma: Can We Use an Old Drug to Learn New Tricks?

Erin Dickerson, PhD; University of Minnesota

After noting that human patients taking the beta-blocker propranolol for heart disease had reduced cancer progression and mortality from angiosarcoma, additional study showed that propranolol is cytostatic, which means it slows or stops growth but does not kill cancer cells. The proposed mechanism of action involves preferential sequestration of propranolol over doxorubicin inside cell storage compartments called lysosomes. Once relocated into the cytoplasm, doxorubicin is more effective at killing malignant cells. Synergy between these two drugs has been demonstrated in several cell lines in vitro. CHF is now funding a multi-institutional clinical trial to evaluate the use of propranolol, in combination with surgery and chemotherapy, to treat canine hemangiosarcoma.

CURRENT CHF GRANTS
• 02534: Clinical Trial for Evaluation of Propranolol and Doxorubicin in the Treatment of Canine Hemangiosarcoma
• 02234-MOU (Co-investigator): A Novel Approach for Prevention of Canine Hemangiosarcoma

Two Decades of Advances in Canine Hemangiosarcoma. The Light at the End of the Tunnel is Getting Brighter, and It's Not a Train!

Jaime F. Modiano, VMD, PhD; University of Minnesota

After decades of research, Dr. Modiano offered the following insights about canine hemangiosarcoma:

• Despite reported breed predilections, there are no significant differences in the molecular properties of hemangiosarcoma among different dog breeds or different tumor locations (spleen vs heart). This confirms that hemangiosarcoma is an indiscriminate cancer of concern for all dogs.
• Hemangiosarcoma is difficult to kill because tumor cells comprise as little as 50% of the total population of cells in the tumor. Effective treatment must address the tumor cells and the surrounding microenvironment. Dr. Modiano’s lab developed the drug eBAT, which makes the tumor microenvironment inhospitable and eliminates sarcoma stem cells.
• Phase 3 of the Shine On Project, in collaboration with the Golden Retriever Foundation, American Boxer Charitable Foundation, and the Portuguese Water Dog Foundation, is nearing complete enrollment. The goal of this phase is to combine early detection and prevention tools to lessen the impact of this deadly cancer.

CURRENT CHF GRANTS
• 02655-E: 2019 Clinician-Scientist Fellowship - University of Minnesota
• 02234-MOU: A Novel Approach for Prevention of Canine Hemangiosarcoma

 

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Genetics & Genetic Testing

Harmonization of Genetic Testing and Breed-Specific Resources

Brenda Bonnett, DVM, PhD; International Partnership for Dogs

CHF, along with the Orthopedic Foundation for Animals (OFA) and other founding partners, provided support for the Harmonization of Genetic Testing for Dogs initiative of the International Partnership for Dogs in 2017 to address the need for objective guidance about genetic test reliability and quality. The initiative’s website, www.dogwellnet.com, provides practical information to address the challenges associated with canine DNA testing – such as what tests to use, how should results be interpreted in light of the bigger picture for a particular dog breed, and more. CHF has continued to provide financial support for this initiative and the database currently contains information on 69 genetic test providers and more than 300 tests and diseases in over 500 different dog breeds and breed types.

CURRENT CHF GRANT – 02328-A: Harmonization of Genetic Testing for Dogs

Cardiac Disease of Purebred Dogs - Genetics & Beyond

Joshua A. Stern, DVM, PhD, DACVIM (Cardiology); University of California, Davis

Dr. Stern reviewed his research into the heritability patterns and causative mutations for common canine heart diseases such as sub-aortic stenosis, pulmonic stenosis, atrial fibrillation, and dilated cardiomyopathy. Genome wide assessment studies (GWAS) and whole genome sequencing (WGS) studies are underway in his laboratory to refine our understanding of these diseases in various dog breeds.

Dr. Stern notes that true cardiac clearances require auscultation and echocardiogram, which can detect early or mild disease. He also recommends that all breeders use the new OFA Advanced Cardiac Database which screens for congenital and adult-onset cardiac disease. The new database also requires mandatory data submission, resulting in more robust and accurate statistics on healthy and affected dogs in comparison to the prior voluntary submission paradigm.

CURRENT CHF GRANTS
• 02327-MOU: Identification of Genetic Markers for Familial Subvalvular Aortic Stenosis in Bullmastiffs
• 02388-MOU: Genetic Markers for Familial Subvalvular Aortic Stenosis in Newfoundlands
• 02520-MOU: Identification of Genetic Markers for Familial Subvalvular Aortic Stenosis in Rottweilers
• 02521-MOU: Identification of Genetic Markers for Familial Subvalvular Aortic Stenosis in Golden Retrievers
• 02424: Identification of Genetic Variants Associated with Pulmonary Valve Stenosis in Bulldogs through Whole-Genome Sequencing

Understanding Dog Breeds as Populations

Jerold S. Bell, DVM; Tufts University and Freshwater Veterinary Hospital

The most common genetic diseases seen in veterinary practice – allergies, hip dysplasia, patellar luxation, heart disease, hereditary cancers, and more – are the result of ancient genetic mutations that occurred well before the development of modern dog breeds. Breed-specific genetic disorders are due to more recent mutations. To preserve genetic and phenotypic health, dog breeders must purposefully select for moderation away from extremes that cause disease.

• Learn more from the RACE-approved webinar “A Clinical Genetics Approach to Understanding Genetic, Multiplex and Health Testing” at https://www.vetvine.com/article/377/akcchf-clinical-genetics.
• Read Dr. Bell’s white paper “Understanding Breeds as Populations” here.

 

Development and Utilization of a Genetic Risk Assessment for a Multifactorial Disease

Leigh Anne Clark, PhD; Clemson University

Dr. Clark’s laboratory is responsible for illuminating the complex genetic traits of the multi-factorial disease Dermatomyositis in Collies and Shetland Sheepdogs. Mutations in three different major histocompatibility complex genes and environmental factors influence the phenotypic expression of this disease. After more than a decade of research, Collie and Sheltie breeders now have a reliable risk tool to inform breeding strategies that will help produce puppies with low-risk genotypes. Dr. Clark’s presentation outlined the challenges of genetic testing and research for complex heritable conditions.

CURRENT CHF GRANTS
• 02654-E: 2019 Clinician-Scientist Fellowship - Clemson University
• 02263-MOU (Co-investigator): Characterization of Kidney Disease in Dalmatians

The Canine Health Information Center (CHIC) Program – Status Update and Call to Action

Eddie Dziuk, MBA; Orthopedic Foundation for Animals Chief Operations Officer

The Orthopedic Foundation for Animals (OFA) maintains a health screening database and a DNA repository. Most of the repository samples represent young, healthy dogs at the time of the sample collection. Therefore, owners of dogs with DNA samples in the Canine Health Information Center DNA repository should update each dog's health data as they age. This allows DNA samples to be matched with the appropriate researchers. Please remind dog owners to e-mail ofa@offa.org with each dog's name, CHIC number, and updated diagnoses or visit www.caninehealthinfo.org for more information.

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Working together, veterinary professionals and CHF can improve the health and well-being of all dogs. CHF, its funded investigators, breeders, veterinarians, and dog owners all benefit from collaboration and an improved understanding of the mechanisms that cause disease in dogs. CHF’s mission is to advance the health of all dogs and their owners by funding sound scientific research and disseminating health information to prevent, treat and cure canine disease. Veterinary professionals like you are critical to implementing new discoveries and educating dog owners. Thanks to you – all dogs have a chance to live longer, healthier lives.