Pug Health Research Projects Update

Research projects are those which the PDCA has elected to support monetarily through health fund donations. The following information comes from brief update reports to the PDCA from each individual study. Studies are subsidized through grants from the AKC Canine Health Fund, the Morris Animal Foundation, and others as noted.

This is an Ohio State University study funded by the Morris Animal Foundation

This is NOT A FINAL REPORT. Updated August 2013.

Grant D09CA-060: Studying How Mast Cell Tumors Spread, Cheryl A. London, DVM, PhD, The Ohio State University

UPDATE: Mast cell tumors (MCTs) are the most common skin tumors in dogs and despite advances in treatment, dogs with aggressive MCTs ultimately develop metastasis and die. As such, new therapies are needed to improve survival rates. In previous studies, researchers from the Ohio State University discovered that amounts of a small piece of genetic material, microRNA (miR-9), were significantly increased in aggressive MCTs in dogs. Interestingly, miR-9 has been linked to metastatic behavior of breast cancer in humans. It is possible that miR-9 also plays a significant role in canine malignant mast cell disease.

In this study, funded by Morris Animal Foundation, the research team is focusing on the overexpression of miR-9 in the development of aggressive MCTs. So far, they have generated mast cells that overexpress miR-9 in the laboratory. Using this molecular tool, they are conducting a thorough analysis of the biological role of miR-9 in aggressive tumors. Their goal is to identify molecular processes affected by miR-9 and to identify potential drug targets to inhibit these processes.

This research will provide a more detailed understanding of the process of metastasis of canine MCTs, thereby generating new otential targets for treatment. The results may also provide information that would help in the development of a diagnostic tool to identify tumors that are more likely to metastasize and need aggressive therapy. These studies will benefit all dogs with MCTs and would be particularly beneficial for breeds at higher risk of MCT, including Shar-peis, Labrador and Golden Retrievers, and Vizslas.

This is a University of Georgia study funded by the AKC Canine Health Fund

This is NOT A FINAL REPORT. Updated April 2013.

Grant 01455: Mapping Genes Associated with Necrotizing Meningoencephalitis in Dogs, Dr. Renne Barber, DVM, University of Georgia

UPDATE: Necrotizing meningoencephalitis (NME) is an important disorder of small breed dogs. NME causes severe inflammation and damage in the brains of affected dogs. The cause of this inflammation is not known, and these dogs often die quickly because the ideal treatment has not yet been determined. Although many factors may contribute to whether or not a dog gets NME, we believe that certain dogs have changes in their DNA that predispose them to developing this disease. Our work focuses on determining what genetic factors contribute to the development of NME, particularly in the Pug, Maltese and Chihuahua. We hypothesize that using currently available genetic tools, we can identify specific alterations in DNA that cause dogs to develop NME.

We began our genetics studies by comparing DNA from Pug dogs with NME to DNA from healthy, control Pug dogs. This preliminary study identified 2 broad regions of DNA that may predispose to the development of NME if altered. The main objectives of our current work are: 1) to further evaluate these initial findings in Pug dogs and 2) to identify the specific changes within these regions of DNA that contribute to disease development in Pugs, Maltese and Chihuahuas. To date, we have done extensive analysis of our initial findings in Pug dogs. We have confirmed that there are two regions of DNA (on chromosomes 8 and 12) that are statistically associated with the development of NME. These findings are a critical first step in sorting out the genetics of NME and have been published in the Journal of Heredity. We also have done a preliminary genetics study in Maltese and Chihuahuas that suggests that these breeds also have a change in their DNA on chromosome 12 that contributes to NME development. Additional dogs of the Chihuahua and Maltese breed need to be evaluated so we can find the specific genetic mutation or mutations on chromosome 12 that are leading to disease development.

This is a Cornell University study funded by the Morris Animal Foundation

This is NOT A FINAL REPORT. Updated February 2013.

Grant D09CA-019: Development of a New Diagnostic Test (Anti-Müllerian Hormone) for Non-Surgical Evaluation of Spay Status and Ovarian Remnant Syndrome, Ned J Place, MD, PhD

UPDATE: For many female dogs and cats, the lack of a visible surgical scar makes it difficult to determine if they have been spayed. Because most shelters require an animal to be spayed before it can be adopted out, animals often require exploratory surgery to determine their spay status. To address this issue, researchers from Cornell University, funded by Morris Animal Foundation, are developing a nonsurgical test to reliably and economically determine the spay status of dogs and cats. The test will measure anti-Müllerian hormone (AMH), a specific ovary-produced hormone that is readily detected in blood samples taken from intact female dogs and cats.

To date, researchers have collected and archived blood samples from dogs and cats that have a known presence or absence of ovaries. These samples will be used as controls for testing the new assay and for evaluating its sensitivity and specificity. Researchers are also in the process of producing recombinant (genetically engineered) canine AMH, which in turn will be used to generate antibodies for use in the new test. They have successfully sequenced canine AMH messenger RNA (mRNA), which transfers the genetic information from DNA to protein, an important first step toward the production of canine AMH protein.

Staff changes delayed the production of antiserum against AMH; however, antibody production is moving forward again. There is a high likelihood that the antibodies for canine AMH will detect feline AMH, and thus the test should work in cats and dogs. The new test is also meant to help diagnose ovarian remnant syndrome-an uncommon situation in which a bit of ovary is left behind after surgery and may cause a spayed animal to go into heat. Projected completion and results of the study are expected by fall 2013.

A nonsurgical diagnostic test that measures AMH in dogs and cats will help veterinary clinicians and shelter personnel to clearly determine an animal's spay status, thereby reducing unnecessary exploratory surgeries and associated costs.

This is an Animal Health Trust (UK) study funded by the Morris Animal Foundation

This is NOT A FINAL REPORT. Updated February 2013. Prior update: June 2012.

Grant D12CA-803: Deriving Canine Induced Pluripotent Stem Cells for Future Therapeutic Use and Disease Modelling, Deborah J Guest, BSc, PhD

PROGRESS UPDATE: Stem cells offer promise for treating many orthopedic, neurologic and cardiovascular injuries and diseases in dogs. To date, induced pluripotent stem cells (iPSCs) have been derived from humans, mice, monkeys, pigs and horses by reprogramming adult cells back to an embryonic state, thereby giving them the potential to develop into any cell type. One advantage of iPSCs is that because they are genetically identical to the patient's cells, there is no risk that they will be rejected by the patient's immune system.

With Morris Animal Foundation funding, researchers from Animal Health Trust are determining the factors and culture conditions required to generate canine iPSCs in the lab. So far, they have reprogrammed adult dog cells into cells that have the appearance of iPSCs, and they are now beginning to analyze and characterize them. The next step is to confirm that these cells express markers of stem cells and have the potential to turn into multiple cell types. Final results are expected by the end of 2013.

If the results are positive, canine iPSCs will prove to be a valuable tool for treating dogs with inherited and acquired diseases. Information gained from this study will form the basis of future work to determine the therapeutic potential of iPSCs to help improve the health and welfare of dogs suffering from a wide range of conditions and injuries.

This is NOT A FINAL REPORT. Updated March 2011. This is the University of Wisconsin-Madison study funded by the Morris Animal Foundation Grant No: D07CA-055 on managing pain after major surgeries, such as amputations.

PROGRESS UPDATE: Pain management is critical to an animal's recovery and quality of life after surgery. With major surgeries, such as limb amputations, effective pain relief is required for several days after surgery. Although fentanyl patches have been used in animals that need pain control for more than several hours, the amount of pain relief provided by fentanyl patches varies dramatically among patients, and the patch can take up to 24 hours to have an effect after placement. Researchers at the University of Wisconsin are studying a novel formulation of the drug hydromorphone, which may last three to four days after a single injection given under the skin. If this drug provides effective pain relief after a single dose, it may allow hospitalized patients to be discharged to their owners more quickly after major surgery. To date, patient enrollment is complete and data analysis is under way. Early review of the data suggests that the new hydromorphone formulation outperforms the standard-of-care analgesic being used as a control—fewer dogs treated with hydromorphone have required additional medications for pain control. Researchers are currently developing the product for commercial use with hopes that this new drug formulation of hydromorphone will offer veterinarians a more effective means of treating postsurgical pain.