Principal Investigator: Dr. Gary S. Johnson, DVM PhD; University of Missouri, Columbia
Total Grant Amount:  $84,121.00; Grant Period:  5/1/2016 - 10/31/2017

Abstract:
Epilepsy is one of the most common neurologic diseases of dogs and a top concern of dog breeders.  Despite strong evidence that genetics is important in determining the risk of idiopathic epilepsy, numerous gene mapping studies have failed to identify a locus that accounts for that risk in either dogs or humans. Seizures occur when excessive activity goes beyond the normal threshold for brain function, many factors contribute to that level of activity, and therefore, mutations in numerous genes may collectively contribute to increased activity until that threshold is exceeded, resulting in epilepsy. Any one of these mutations may be present in non-epileptic dogs, but because it only partially alters activity, it would not produce seizures. Therefore, traditional gene mapping studies might overlook that mutation. Using a novel whole genome sequencing approach the investigators hope to identify DNA variations in epileptic dogs that could affect the function of genes such as ion channels and neurotransmitter receptors that have been shown to alter the seizure threshold in humans or rodents. The frequency of such variations in populations of epileptic and non-epileptic dogs will be directly compared rather than the indirect markers used in traditional mapping studies. The increased power provided by looking for specific gene candidate variations rather than linked markers will aid the identification of epilepsy risk factors, perhaps leading to development of DNA tests to enable breeders to select against such risk factors.

02275:  Disease Risks Associated with Spay and Neuter: A Breed-Specific, Gender-Specific Perspective
Principal Investigator: Dr. Benjamin L Hart, DVM, PhD; University of California, Davis
Total Grant Amount:  $61,784.00; Grant Period:  9/1/2016 - 8/31/2017

Project Abstract:
This study extends the investigator’s recently completed AKC Canine Health Foundation-funded project studying 12 dog breeds to identify major differences in the degree to which spay or neuter may be related to an increase in joint disorders (hip dysplasia; cranial cruciate ligament tear) and/or cancers (lymphoma; hemangiosarcoma; and mast cell tumor). The original breeds studied were: Labrador Retriever, Golden Retriever, German Shepherd Dog, Rottweiler, Boxer, Bulldog, Doberman Pinscher, Dachshund, Corgi (both breeds), Chihuahua, Yorkshire Terrier and Shih Tzu. Findings did not associate an increase in disease association in the small breeds with spaying or neutering, while in larger breeds disease risk was dependent upon gender, and whether the spay or neuter procedure was performed before or after one year of age (Hart, B.L., L.A. Hart, A.P. Thigpen and N. H. Willits. 2014. Long-term health effects of neutering dogs: Comparison of Labrador Retrievers and Golden Retrievers. PLoS ONE 9(7): 10.1371/journal.pone.0102241).

In this second phase, the following breeds have been added to the study: Great Dane, Australian Shepherd, Bernese Mountain Dog, Cocker Spaniel, Border Collie, Beagle, St. Bernard, Irish Wolfhound, Jack Russell Terrier, Pug, Maltese, Pomeranian, Miniature Schnauzer, Boston Terrier, Australian Cattle Dog, Shetland Sheepdog, English Springer Spaniel, Cavalier King Charles Spaniel, and West Highland White Terrier. Upon completion of the study, the major publisher, Wiley, has agreed to place the total data set of all 31 breeds on an open access website as a resource for breeders, dogs owners, researchers and veterinarians.

 

Principal Investigator: Erin B Dickerson, PhD, University of Minnesota
Total Study Cost: $172,431; Grant period: 10/1/2016 – 9/30/2018

Project Abstract:
Hemangiosarcoma is an aggressive and almost uniformly fatal cancer of dogs. Researchers uncovered evidence that a common cellular signaling pathway is associated with aggressive hemangiosarcoma tumor growth and chemotherapy resistance. Signaling pathways are coordinated chemical activities in a cell that collectively control one or more cell functions. Abnormal activation of signals often trigger or facilitate the development of diseases, including cancer. Researchers will investigate how signaling pathways contribute to hemangiosarcoma growth, and if existing drugs can interrupt the process to reduce tumor growth and chemotherapy resistance. Finding a new approach to treat canine hemangiosarcoma is a vital step in improving survival rates in dogs with this aggressive cancer.

Principal Investigator: Dr. Benjamin L Hart, DVM, PhD; University of California, Davis
Total Grant Amount:  $61,784.00; Grant Period:  9/1/2016 - 8/31/2017

Project Abstract:
This study extends the investigator’s recently completed AKC Canine Health Foundation-funded project studying 12 dog breeds to identify major differences in the degree to which spay or neuter may be related to an increase in joint disorders (hip dysplasia; cranial cruciate ligament tear) and/or cancers (lymphoma; hemangiosarcoma; and mast cell tumor). The original breeds studied were: Labrador Retriever, Golden Retriever, German Shepherd Dog, Rottweiler, Boxer, Bulldog, Doberman Pinscher, Dachshund, Corgi (both breeds), Chihuahua, Yorkshire Terrier and Shih Tzu. Findings did not associate an increase in disease association in the small breeds with spaying or neutering, while in larger breeds disease risk was dependent upon gender, and whether the spay or neuter procedure was performed before or after one year of age (Hart, B.L., L.A. Hart, A.P. Thigpen and N. H. Willits. 2014. Long-term health effects of neutering dogs: Comparison of Labrador Retrievers and Golden Retrievers. PLoS ONE 9(7): 10.1371/journal.pone.0102241).

In this second phase, the following breeds have been added to the study: Great Dane, Australian Shepherd, Bernese Mountain Dog, Cocker Spaniel, Border Collie, Beagle, St. Bernard, Irish Wolfhound, Jack Russell Terrier, Pug, Maltese, Pomeranian, Miniature Schnauzer, Boston Terrier, Australian Cattle Dog, Shetland Sheepdog, English Springer Spaniel, Cavalier King Charles Spaniel, and West Highland White Terrier. Upon completion of the study, the major publisher, Wiley, has agreed to place the total data set of all 31 breeds on an open access website as a resource for breeders, dogs owners, researchers and veterinarians.

Click on this link to be redirected to the AKC Canine Health Foundation portfolio of research grants.

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Grant Amount: $46,358

 Dr. Laura E. Selmic, BVetMed, University of Illinois

 January 1, 2016 - December 31, 2017

Abstract

Surgery is the primary treatment for many common tumors affecting dogs including mammary tumors and soft tissue sarcomas (STS). For these tumors, the best chance of cure is offered if the surgeon can fully remove both visible and microscopic traces of the tumor. Unfortunately, to do this, surgeons must rely on indirect and crude methods to assess the extent of the tumor during surgery. The success of the procedure will not be known until several days later, following sample assessment by the pathologist. After surgery, decisions regarding the necessity of further treatment and the patient’s prognosis are often determined from the pathology results. For malignant tumors, if the disease is minimally or incompletely removed, further surgery or radiation therapy is often required. Additional treatments such as these can result in further risk and discomfort for the patient as well as present emotional and financial costs for owners. Optical coherence tomography (OCT) is an emerging diagnostic imaging tool that uses light waves to generate real-time, high-resolution images of tissue at a microscopic level. These images can be used to evaluate for residual disease at the time of surgery giving immediate feedback to the surgeon. This study will focus on validating this technology for the imaging of surgical margins of two important canine cancers - mammary tumors and STS. If successful, this technology can be used to assess for residual cancer during surgery to benefit patients by guiding accurate treatment recommendations and attempting to reduce the need for additional treatments or surgery, and thus advancing the standard of care for canine patients.



CHFlogoflagPrincipal Investigator: Dr. Cynthia M. Otto, DVM PhD; University of Pennsylvania
Total Grant Amount:  $11,340.00; Grant Period:  12/1/2015 - 11/30/2016

Project Abstract:
As the investigators wrap up the 14th year of the 9/11 Medical Surveillance Study, they continue to follow 2 surviving deployed dogs and 1 surviving control dog, each of them now 16 years of age. The initial study group consisted of 95 deployed and 55 non-deployed Search and Rescue dogs. Findings to date indicate that overall these dogs have demonstrated good longevity and quality of life. This final phase of the study will monitor the remaining dogs, placing emphasis on health issues occurring in later years of life and necropsy evaluations at time of death. This vital information will allow for a comprehensive understanding of the impact of the deployment and a life spent working Search and Rescue on long-term canine health.

The rate of cancer in deceased deployed dogs to date is not different than in deceased control dogs. Of note, within the deployed dogs, the median age at death was significantly lower for dogs with cancer than the non-cancer group; however, this was not the case with the control group. As the final three dogs approach the end of their natural lives, the investigators will further define any effects of the 9/11 deployment in the full cohort of study dogs.  As they analyze the data, a full picture of causes of death and types and incidences of cancer, and long-term impacts of the 9/11 deployment may become clear. The ability to see this study through to completion and publish the long term findings will provide critical information to canine health that may affect future tactics employed in Search and Rescue missions.

The AKC CHF is proud to have funded Dr. Otto through all the years of this important work on behalf of Search and Rescue dogs from its inception in 2001.

CHFlogoPrincipal Investigator: Dr. Erin B. Dickerson, PhD; University of Minnesota
Total Grant Amount:  $86,206.00; Grant Period:  1/1/2016 - 12/31/2017

Project Abstract:
Hemangiosarcoma is an extremely aggressive cancer that is rapidly fatal in dogs. While the lifetime risk is alarmingly high for some breeds such as Golden Retrievers and German Shepherd Dogs, the disease does not discriminate, and it can strike any dog at any time. Despite considerable efforts by veterinarians and scientists to find effective treatments, the outcome for dogs with hemangiosarcoma has changed very little over the past few decades. Recent evidence provides essential clues into how these tumors grow and progress, generating new ideas for treatment approaches. Such new evidence suggests that hemangiosarcoma cells rely on the metabolism of lipids or fatty acids to supply energy for tissue invasion or continued tumor growth. To obtain these lipids, hemangiosarcomas may take over the metabolic machinery of neighboring cells, forcing them to produce nutrients for the tumor cells to help them proliferate and grow. This study will verify that tumor cells rely on lipid metabolism for growth, and determine if tumor cells alter the metabolism of fat cells to obtain cellular nutrients and accelerate tumor cell lipid metabolism.  Identifying and exploiting a novel mechanism that may disrupt this process by inhibiting the interactions between tumor cells and cells in the tumor environment will speed clinical investigations, and ultimately lead to improved outcomes for dogs with this devastating disease.

CHFlogoPrincipal Investigator: Dr. Jonathan D Foster, VMD; University of Pennsylvania
Total Grant Amount:  $11,493.36; Grant Period:  11/1/2014 - 10/31/2015

Project Abstract:
Acute kidney injury (AKI) is a devastating disease in canine patients. AKI represents a spectrum of disease characterized by a rapid loss of kidney function, resulting in impaired kidney filtration of metabolic waste products. Regardless of the inciting injury, the resulting kidney dysfunction causes increased serum kidney values and often decreased urine production. The resulting retention of metabolic waste products causes the clinical illness of AKI. Decreased urine production (oliguria) or complete cessation of urine production (anuria) may indicate a more severe kidney injury and are associated with increased mortality. Patients with decreased urine production are more difficult to manage when hospitalized and have higher morbidity than patients with normal urine output. Therapeutic intervention with diuretics has historically been performed in an attempt to induce urine production and thus facilitate the filtration and excretion of metabolic wastes. Unfortunately these therapies are often ineffective and are not without risk of unwanted side effects. Fenoldopam (a selective dopamine DA-1 receptor agonist that induces renal vasodilation) has recently been shown to increase urine production in people with minimal side effects. Little is known regarding the effect of the drug on kidney filtration and whether there is potential for its use in dogs. The purpose of this study is to determine the effect of fenoldopam on kidney filtration by measuring glomerular filtration rate during fenoldopam administration. If fenoldopam increases filtration rate it may in turn facilitate removal of metabolic waste products, potentially leading to improved outcome in patients with AKI and decreased urine production.

CHFlogoGrant Amount: $12,960
Dr. Christine A Petersen, DVM PhD, University of Iowa
October 1, 2015 - September 30, 2016
Breed(s): All Dogs

Abstract
Recent studies show the presence of resistant infections in dogs and the ability of these infections to spread between a dog and its family. New treatment options are needed, and development of non-antibiotic antibacterial agents, or immunotherapy, is critical to progressing treatment for potentially fatal infections. This project will use cutting edge immunology to better understand how special regulatory immune cells (B10 B cells) in hunting Foxhounds with naturally-occurring Leishmania infections might be reprogrammed to help fight infections. These unique immune cells are thought to alter the course of human diseases such as malaria, lupus, and arthritis. Dogs have an immune system very similar to humans and, unlike mice, represent a way to investigate and further understand these cells in naturally-occurring infections in dogs; findings that will also translate to human health. This innovative research will expand our understanding of how regulatory B cells could be modulated to control infections, ameliorate canine allergy and dampen autoimmune diseases like lupus and thyroid disease, and thus may also identify targets for much-needed new therapies for dogs.

CHFlogoGrant Amount: $12,952 (still funded)
Dr. Angela M Arenas, DVM, PhD, Texas A&M AgriLife Research
October 1, 2015 - September 30, 2016
Breed(s): -All Dogs

Abstract
Brucella infections constitute a serious problem for dog breeders, pet owners, and kennels, leading not only to economic costs associated with reproductive loss, but also a public health concern because of the zoonotic potential. The disease, once established, is difficult to control due to the lack of a protective vaccine for canine use. Historically, brucellosis control efforts have demonstrated that the spread of the disease is preventable or significantly reduced in association with vaccination. Unfortunately, efforts to develop a brucellosis vaccine that is safe and effective for dogs have been unsuccessful to date. The goal of this research is to develop a safe and efficacious Brucella canis vaccine using a genetic mutant that has been shown to be safe and efficacious for controlling infection against other Brucella species. The development of a safe and highly protective brucellosis vaccine for dogs will significantly impact canine and human health by limiting the spread of disease.

CHFlogoGrant Amount: $119,268
Dr. Karin Allenspach, DVM PhD, Royal Veterinary College, University of London
October 1, 2014 - December 31, 2015
Sponsor(s): American Shih Tzu Club, Inc., Chow Chow Club, Inc., Collie Health Foundation, English Setter Association of America, Inc., Gordon Setter Club of America, Inc., Great Pyrenees Club of America, National Shiba Club of America, Portuguese Water Dog Foundation, Tibetan Terrier Club of America/Tibetan Terrier Health & Welfare Foundation, Treeing Walker Breeders & Fanciers Association, Versatility in Poodles, Inc.
Breed(s): German Shepherd Dog
Research Program Area: Immunology and Infectious Disease

Abstract: Inflammatory Bowel Disease (IBD) is a group of disorders in which the intestinal tract has become invaded with the dog's own white blood cells leading to inflammation. Over time, this inflammation causes the intestine to become less efficient at absorbing nutrients from digested food and weight loss, and vomiting or diarrhea often result. IBD can be controlled, but not cured. The cause of IBD is poorly understood, but it appears that genetics, diet, intestinal bacteria, and abnormalities of the dog's immune system all play a role. Dr. Allenspach has recently identified genetic markers known as SNPs (single nucleotide polymorphisms) which she believes contribute to disease susceptibility. Beyond genetics, this research group has mechanistic data showing one of the putative mutations contributes to the inflammation seen in the intestine of dogs with IBD. In order to find all underlying genetic factors that could contribute to disease, they propose to perform a genome-wide association study. This study will lead to the development of new diagnostic and therapeutic avenues for canine IBD as has already been the case in people with IBD.

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Grant Amount: $360,933
Dr. Jaime F Modiano, VMD PhD, University of Minnesota
January 1, 2014 - December 31, 2016

Sponsor(s): American Belgian Tervuren Club, Inc., English Setter Association of America, Inc., German Shorthaired Pointer Club of America, Great Pyrenees Club of America, Labrador Retriever Club, Inc., Portuguese Water Dog Foundation, Rottweiler Health Foundation, United States Australian Shepherd Association, United States Australian Shepherd Foundation
Breed(s): Golden Retriever
Research Program Area: Oncology - Lymphoma

Abstract: Lymphoma and hemangiosarcoma are major health problems in Golden Retrievers, causing both suffering and premature death. Through ongoing collaboration, Drs. Jaime Modiano, Matthew Breen, and Kerstin Lindblad-Toh have identified several regions of the genome that contain genetic heritable risk factors for lymphoma and hemangiosarcoma in Golden Retrievers. They have tumor-specific mutations that occur recurrently in both cancers, some of which are linked to duration of remission when treated with standard of care. Their results indicate that a few heritable genetic risk factors account for as much as 50% of the risk for these cancers. These findings offer the potential to develop tests and strategies for DNA tests that can predict risk for individual dogs, as well as to manage risk across the population as a whole. Indeed, both the inherited risk factors and tumor mutations point to pathways that have been implicated in the pathogenesis of lymphoma and hemangiosarcoma, and thus should inform the development of targeted therapies. In the current study, Drs. Modiano, Breen, and Lindblad-Toh will find the precise mutations for the heritable genetic risk factors and to validate markers (mutations) used to determine risk at the heritable loci in a larger independent population of Golden Retrievers from the United States and from Europe in order to develop robust risk prediction tools and an accompanying DNA test. Further, they will identify and characterize tumor mutations and study their relationship to the heritable risk factors, tumor pathogenetic mechanisms, and disease outcome.

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02110-A:  Investigating the Effects of an Infusion of Fenoldopam on Kidney Function to Improve Outcomes of Acute Kidney Injury Patients
Principal Investigator: Dr. Jonathan D Foster, VMD; University of Pennsylvania

Project Abstract:
Acute kidney injury (AKI) is a devastating disease in canine patients. AKI represents a spectrum of disease characterized by a rapid loss of kidney function, resulting in impaired kidney filtration of metabolic waste products. Regardless of the inciting injury, the resulting kidney dysfunction causes increased serum kidney values and often decreased urine production. The resulting retention of metabolic waste products causes the clinical illness of AKI. Decreased urine production (oliguria) or complete cessation of urine production (anuria) may indicate a more severe kidney injury and are associated with increased mortality. Patients with decreased urine production are more difficult to manage when hospitalized and have higher morbidity than patients with normal urine output.

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Gastric dilatation-volvulus (GDV) is a common medical and surgical emergency that involves severe gas distention and malposition of the stomach in dogs. GDV results in profound distension of the stomach which compresses vital blood vessels and organs within the abdomen, thus reducing oxygen delivery to these organs. The ultimate result is tissue death and toxins in the blood stream. Surgery is necessary to correct the condition, and overall mortality rates range from 10-50% depending on severity and duration of gastric dilatation. For this reason, rapid and effective decompression of the stomach is critical for successful treatment of dogs with GDV.  Read more

 

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Lymphoma and hemangiosarcoma are major health problems in Golden Retrievers, causing both suffering and premature death. Through ongoing collaboration, Drs. Jaime Modiano, Matthew Breen, and Kerstin Lindblad-Toh have identified several regions of the genome that contain genetic heritable risk factors for lymphoma and hemangiosarcoma in Golden Retrievers. They have tumor-specific mutations that occur recurrently in both cancers, some of which are linked to duration of remission when treated with standard of care.

Their results indicate that a few heritable genetic risk factors account for as much as 50% of the risk for these cancers. These findings offer the potential to develop tests and strategies for DNA tests that can predict risk for individual dogs, as well as to manage risk across the population as a whole. Indeed, both the inherited risk factors and tumor mutations point to pathways that have been implicated in the pathogenesis of lymphoma and hemangiosarcoma, and thus should inform the development of targeted therapies.

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Chronic kidney disease (CKD) is a significant cause of illness and death in dogs and is often due to glomerular diseases. Dogs with glomerular disease often have poor outcomes with standard therapy, and specific treatment recommendations are difficult without performing a kidney biopsy to determine the type of glomerular disease present, since treatment and outcome among these diseases differs substantially. Even then, we lack an understanding of the mechanisms driving these diseases, limiting our ability to optimally treat these dogs. Therefore, tests to non-invasively diagnosis the type of glomerular disease would help veterinarians more appropriately treat these patients and provide insight into the mechanisms that cause the diseases.

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Regenerative medicine is a rapidly developing field with the potential to transform the treatment of canine disease. The ability to repair damaged tissue and treat diseases once believed to be incurable may soon be a reality. However, there are concerns that some techniques are being used prematurely. Due to the lower regulatory barriers in veterinary medicine, company-sponsored regenerative medicine products and techniques are currently used in general practice and specialty hospitals without the benefit of having been preceded by stringently controlled, independently funded clinical trials. As a result, techniques vary widely and the evidence that they work is anecdotal at best.

The AKC Canine Health Foundation has made the evidence-based practice of regenerative medicine a major focus within our research portfolio. Through an ongoing commitment to fund research studies that will inform the veterinary community in the use of safe and effective regenerative medicine techniques, we intend to protect dog owners and support veterinarians with innovative technology that will consistently improve outcomes for dogs. In support of our effort to provide evidence-based regenerative medicine research, CHF is funding this landmark study to evaluate the effectiveness of Platelet-Rich Plasma (PRP) and stem cells in the treatment of the most common sporting injury in dogs: supraspinatus tendonopathy (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.

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Most dogs in the United States are spayed or neutered, and the default recommendation has been to perform these elective surgeries prior to physical maturity. However, recent data suggest that early spay and neuter may adversely impact the health and well-being of dogs.

In preliminary studies funded by CHF, Dr. Ben Hart of the UC Davis College of Veterinary Medicine found that early spay or neuter, prior to 12 months of age, was related to a significant increase in risk in five diseases of concern: hip dysplasia; cranial cruciate ligament tear; lymphosarcoma; hemangiosarcoma; and mast cell tumor. CHF has now funded the second phase of Dr. Hart's research in which he will expand his work to consider breed differences in vulnerability to joint disorders and risks of various cancers after early or late spay/neuter. Breeds considered will include: Labrador Retrievers, German Shepherd Dogs, and Dachshunds. Rottweilers, Chihuahuas, Standard Poodles, and Miniature Poodles will be included if resources and patient data are available. The expectation is that by inclusion of multiple breeds in phase II Dr. Hart will be able to develop a generalized understanding of the impact of early spay and neuter on disease risk in dogs. This in turn will enable veterinarians and breeders to make data-driven recommendations regarding timing of spay/neuter procedures to reduce the risk of development of multiple devastating diseases.

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Epilepsy is a debilitating condition that affects a large number of dogs, resulting in premature death and distress for their owners. For many dogs the underlying cause is unknown. In people, advances in some types of imaging have identified subtle abnormalities, including abnormal development and shrinkage of particular regions in the brain of some people with epilepsy that can be surgically removed to improve the control of seizures. This project will apply the same advanced techniques to the brains of dogs with epilepsy to determine whether those same abnormalities exist in dogs. In those dogs in whom no abnormalities can be found, this project will investigate a new form of treatment, known as neurostimulation which has been shown to reduce the frequency of seizures dramatically in human clinical trials. This involves surgically implanting a new, highly sophisticated device called the Brain Radio that can provide controlled electrical stimulation to parts of the brain while simultaneously recording the brain's activity. This device is one of the very first that could potentially provide successful therapy only when needed to treat imminent seizures and if it proves successful in dogs it will enter clinical trials in people with epilepsy.

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With the growing use of artificial insemination and frozen semen in dog breeding, the level of predictability and odds of fertile matings for any breed of dogs is currently unknown. The objective of Dr. Meyer's study is to determine the relationship of sperm characteristics to pregnancy outcome in a large population of a single breed of valuable service dogs (Labrador Retrievers) in which semen characteristics and known fertility has been tracked for a number of years. Researchers will collect semen samples from 35 Labrador Retriever stud dogs and determine a wide array of semen quality measures. Semen collections will be obtained twice weekly from each of two different males (4 dogs per week) at Guide Dogs for the Blind in San Rafael, CA. Semen will be evaluated at UC Davis using computer-assisted semen analysis, flow cytometry and brightfield and fluorescence microscopy.

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Scientific Title: Allogeneic Stem Cell Therapy as a Treatment for Canine Osteoarthritis

Dr. Kristina M. Kiefer, University of Minnesota, First Award, D15CA-311

Summary: Researchers will investigate the safety and efficacy of using donated stem cells to treat dogs with naturally occurring osteoarthritis that have limited treatment options.

Description: Osteoarthritis is a progressive, degenerative joint disease that afflicts many pets. Although the disease cannot be cured, it can be managed with long-term medication to help reduce joint swelling and associated pain. Some evidence suggests that stem cell therapy may improve the quality of life for pets with osteoarthritis; however, harvesting stem cells requires the patient to undergo general anesthesia.  Not all pets are good candidates for anesthesia, surgery or long-term standard medications. In this clinical trial, researchers will investigate the safety and efficacy of using stem cells donated by healthy dogs to treat dogs with osteoarthritis. If successful, this alternative therapy may improve the quality of life for many pets with limited treatment options.

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Scientific Title: Development of an MHC Class I Tetramer to Study Virus- and Tumor-specific CD8+ T-cell Responses in Dogs

Dr. Paul R. Hess, North Carolina State University, D15CA-015

Summary: Researchers will develop a state-of-the art molecular tool to track and study killer T-cell populations that are responsible for fighting viral infections and cancer in dogs.

Description: In humans, a powerful immunologic reagent called a tetramer is standardly used to visualize changes in the body's killer T-cells.  These cells respond to immunologic challenges and are critical to the body's immune system.  Current knowledge of T-cell behavior in dogs could be significantly advanced with the development of a dog-specific tetramer.  Researchers will work to construct the first canine tetramer, which would then be used in the development of vaccines for infectious diseases and cancer in dogs.

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Canine lymphoma is the most common blood-based cancer in dogs with an estimated annual incidence of 30/100,000. Chemotherapy induces remission in 75-85% of patients; however, the majority of patients relapse with drug-resistant lymphoma within 8-10 months of diagnosis and most dogs die of their disease shortly thereafter.

Cell-based vaccine strategies that stimulate anti-tumor immunity have shown promise in the treatment of many different cancer types including non-Hodgkin's lymphoma (NHL) in humans. In a previous study Dr. Mason developed a cell-based vaccine to induce anti-tumor immunity in dogs with NHL.

Initial studies were hopeful as this early vaccine significantly prolonged second remission duration and overall survival, but ultimately the vaccine did not prevent relapse.

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The Major Histocompatibility Complex (MHC) genes encode proteins that are critical for a wide range of biological functions, from immune protection against infectious disease to the predisposition of an individual to develop diabetes and auto immune diseases.

The MHC genes in the dog are incompletely characterized, thereby severely limiting our ability to full define the cause of many canine diseases. Dr. Ramakrishnan has developed improved methods for identifying the different forms of canine MHC genes in a large number of dogs of diverse breeds.

In this study he will characterize the patterns of MHC genetic variation in over 1200 dogs from at least 50 breeds using a high throughput sequencing strategy. The distribution and frequency of different forms of each of these genes and their specific clustering among different breeds will greatly enhance our knowledge of the genetic diversity among breeds.

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Leukemia represents a range of cancers, most often classified according to the type of blood cell affected and the clinical progression. Leukemia may be chronic, progressing slowly for many years with minimal symptoms, or acute, with sudden onset and rapid progression of symptoms, often resulting in euthanasia.

The true incidence of leukemia in dogs is unknown, but consensus opinion is that many cases remain undiagnosed. In previous studies Dr. Breen found that canine leukemia presents with characteristic chromosomal and genetic changes shared with those known in human leukemia.

In humans these chromosomal and genetic aberrations have been linked to disease progression and response to therapeutics, and in turn, this information drives clinical management of the patient.

In this multicenter study, Dr. Breen's group will use high-resolution genome-wide chromosomal evaluation to screen a large cohort of canine leukemia patients for the presence of recurrent chromosomal and genetic changes.

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Semen is not sterile and cannot be collected without bacterial contamination due to presence of normal bacterial flora on the urethral mucosa. Bacterial growth in stored semen is presumed to be controlled by addition of an extender to the semen, a liquid medium containing nutrients, buffering agents, and antibiotics.

There is evidence in large animal species of varying efficacy of antibiotics in controlling bacterial growth in extended semen, raising concerns about passage of disease through semen. To date there are no studies in the dog documenting control of growth of aerobic and anaerobic bacteria, and mycoplasma through use of antibiotics in commercially available canine semen extenders.

Dr. Kustritz will evaluate whether growth of aerobic, anaerobic and mycoplasma species will be controlled in semen extended with commercial canine extender when held at refrigerator or room temperatures for up to 48 hours. The results will provide practical information to breeders who ship and receive semen.

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 chf-logoGranulomatous colitis is a severe inflammatory bowel disease (IBD), usually diagnosed in young dogs. Affected dogs present with hemorrhagic diarrhea, often progressing to weight loss and debilitation.

Recent studies have identified invasive Escherichia coli (E. coli) bacteria within macrophages in the inflamed large intestine, and eradication of E.coli induces dramatic clinical and histologic improvement.

Unfortunately, the emergence of antimicrobial resistance has greatly reduced our ability to treat this disease, and persistently affected dogs are frequently euthanized.

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Meningiomas are the most common primary brain tumor in dogs that affects more than 10,000 dogs in the U.S. annually. These tumors occur most frequently in older dogs and in certain breeds -- Golden Retrievers, Labrador Retrievers, Boxers, German Shepherd Dogs and Collies -- causing uncontrolled generalized grand mal seizures in most cases. Although the biological behavior of these tumors is generally considered benign, most meningiomas recur less than one year after either surgery or radiation therapy. Furthermore, radiation therapy is expensive, involves many, repeated episodes of general anesthesia, and cause severe adverse effects. Longer survival times can be achieved through special techniques, but most dogs treated undergo more standard surgical removal and/or radiation therapy. Clearly, there is an urgent need for novel therapies to prevent tumor recurrence and increase survival time after surgery.

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Mast cell tumors account for up to 20 percent of all skin cancers in dogs. The research fellow hopes to identify the underlying molecular mechanisms of mast cell tumor and to narrow down the genomic regions that are important in the initiation and progression of this cancer.

Better understanding of the underlying molecular mechanisms of mast cell tumors will provide diagnostic, prognostic or therapeutic benefits for dogs with the disease.

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All dog breeds are susceptible to mammary cancer. Researchers will evaluate the role of citrullination, a cellular process that is mediated by peptidylarginine deiminases (PAD) enzymes, in canine mammary cancer.

PAD activity is usually low in healthy tissues, but it often increases during disease progression, including during breast cancer development. The investigators will study the process of PAD-mediated citrullination in more detail in canine mammary cancer stem cells.

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Canine hemangiosarcoma is a common and highly metastatic cancer that affects all breeds of dogs. These tumors are particularly drug resistant, which makes them difficult to treat.

The investigators recently identified a more drug-resistant cell population in hemangiosarcoma. These cells appear to be extremely efficient in isolating cancer drugs and preventing them from reaching their targets.

The investigators will use several strategies to try to disrupt this process and they will determine whether any of these approaches improves drug responses and diminishes drug resistance.

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Lymphoma is one of the most commonly occurring malignant tumors in dogs. Though treatable, the disease often recurs and spreads.

This study will determine the safety, efficacy and prognostic factors of a cancer-killing virus developed by researchers at the Mayo Clinic.

Researchers at the University of Tennessee have already determined a safe dosing protocol for this virus in healthy dogs, and this clinical trial will test the dosing in dogs with B-cell lymphoma.

Using state-of-the-art cancer imaging, the study team will determine how successfully the virus spreads to sites of cancer. They will also study the dogs’ immune responses to the virus.

FINAL RESULT:  Immunotherapy may revolutionize B-cell lymphoma treatment in dogs

Lymphoma is one of the most common types of malignant cancer. Several types of lymphoma are diagnosed in the
dog, but the majority (approximately 70 percent) arise from transformed B-cells. Unfortunately, in spite of many
advances in chemotherapy protocols, the prognosis for dogs with B-cell lymphoma has not changed significantly in
more than 30 years.

Passive immunotherapy, which uses molecules called antibodies to kill cancer cells, has revolutionized lymphoma
treatment in humans. Morris Animal Foundation-funded researchers at the University of Minnesota, in
collaboration with researchers at Idexx Laboratories, Elanco Animal Health, and Stanford University, investigated
whether or not this type of treatment could translate into helping dogs with cancer. Using recently developed
canine-specific antibodies, the research team evaluated the safety and efficacy of these antibodies in the treatment
of canine B-cell lymphoma. Antibodies were directed against two different targets on the cancer cells, and
investigators believed that a combination of these two antibodies would be effective in treating dogs with B-cell
lymphoma.

The researchers confirmed that the antibody combination promoted the killing of canine lymphoma cells in a
laboratory setting. The research team then used a pre-clinical model to test the combination. Highly encouraging
data suggested that this immunotherapy combination is both safe and effective in treating diffuse large B-cell
lymphoma. The next research step is to shepherd these antibody therapies through regulatory approval and into
canine clinical trials.

Lymphoma is a serious and common canine cancer, affecting dogs of any age or breed. Some breeds, such as
golden retrievers and boxers, have a historically higher risk for the disease. Other commonly affected breeds include
basset hound, Saint Bernard, Scottish terrier, bulldogs, Airedale, Weimaraner, Doberman pinscher, Labrador
retriever, English setter and Great Dane. If proven effective in clinical trials as passive immunotherapy, use of the
antibodies in this study could significantly improve treatment for all dogs with B-cell lymphoma. (D13CA-033)

AGSDCF Purpose

agsdcf_logo_smallThe American German Shepherd Dog Charitable Foundation, Inc. is a non-profit organization devoted to funding research projects that improve the health of the German Shepherd Dog.

We are grateful to the special dogs who have given their hearts and souls to make our daily lives happier. They ask nothing more than to be loved, fed, and their health needs met.

Your donations to this Foundation will help make future generations healthier and happier.

 

    

Contact us:  info@AGSDCF.com

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