2017 Funded Projects

Research Projects funded by the CRF for 2017

 

(1) Distribution of genetic mutations associated with degenerative myelopathy

(Dr Jayne McGhie, University of Queensland)

Canine degenerative myelopathy (DM) is a non-treatable disabling neurodegenerative disorder characterized by progressive motor neuron loss and paralysis that culminates in death (commonly by euthanasia). It affects mature dogs in a range of breeds. Recently a mutation in the canine superoxide dismutase 1 (SOD1) gene has been identified as strongly linked to the disease. Genetic testing offering a means to rapidly identify non-clinically affected dogs that are potentially at risk. This knowledge can be used to make breeding decisions to reduce the incidence of DM.

German Shepherd and related Shepherd breeds have a high incidence of DM. The current project aims to test non clinical working shepherd dogs and associated breeding shepherd populations (including any pups) to: (a) estimate the frequency of the deleterious mutation for DM, together with a selection of other known diagnostic markers of disease in these breeds, and (b) inform future breeding strategies to reduce the incidence of this disease in the population. In collaboration with the Queensland Police Force, we will use state-of-the-art genetic testing equipment (Sequenom) and expertise within the University of Queensland to genotype a random sample of 150-200 working dogs, breeders or pups. Expected outcomes beyond the aims above include development of a testing capability for disease diagnosis and preventative medicine that can be applied across a range of breeds in Australia, longitudinal study of the health and well-being of these working animals, and creation of a genomic biobank of DNA for German Shepherds for future research purposes.

(2) Bacterial vaccine against canine pyometra

(Dr Natalie Krekeler, University of Melbourne)

Pyometra (pus in the uterus) is a life-threatening infectious disease in bitches. Up to 25% of un-spayed bitches develop the disease before they reach ten years of age, and most of them die if they are left untreated. However, even if they are treated, most bitches will lose their reproductive potential, as a surgical intervention (spaying) is often the treatment of choice by veterinarians. Escherichia coli (E. coli) are the bacteria most commonly isolated. So far no preventative measures other than spaying are available. In a previous study we have tested a killed vaccine against certain bacterial virulence factors, which did not lead to the desired antibody response in the animals. This was most likely due to the fact that a killed vaccine was used. We now propose to generate al live-attenuated E. coli vaccine using a novel technique. Inactivating certain virulence genes in these bacterial strains has shown effective in a previous experiment with similar E. coli causing disease in birds. It allows using a live bacterial strain as a vaccine candidate, which is more likely to raise a satisfactory antibody response than a killed vaccine.


(3) A safety trial of next generation cancer vaccines and targeted IL-15 plasmid therapy

(Dr Christopher Weir, Kolling Institute)

Approximately 1 in 3 pet dogs will be diagnosed with cancer in their lifetime. While some canine cancers can be treated with surgery, chemotherapy and radiotherapy, expense and availability may prevent many dogs receiving treatment. Novel immune based therapies provide another potential weapon to fight canine cancer. We have developed a next generation cancer vaccine (NGV). The vaccine presents a patient's own tumour proteins back to the immune system together with a unique stimulant (RZ-1) and an adjuvant (Advax). Pre clinically we have shown this new vaccine approach is superior in efficacy to the currently marketed canine cancer vaccine. We have also developed targeted plasmid IL-15 therapy which is delivered directly into the tumour to stimulate immune cells inside. The next step is to show safety of the NGV with or without IL-15 therapy in canine cancer patients.

Canine patients with externally accessible tumours who have failed or have no option of standard of care therapy will be offered a place in the trial. Dogs will be placed into groups 1) Vaccine only 2) Combined Vaccine and Inter tumoural vaccine 3) IL-15 therapy 4) IL-15 + Vaccine

The dogs will be assessed for adverse reactions to the vaccine/IL 15 therapy during and after the treatment period and monitored for tumour progression or regression. Blood samples will be collected to assess immune cell levels and for cytokine analysis. Dogs showing no adverse reactions to the therapies and perceived benefit will be offered further treatments after a period of 3 to 6 months.

 

(4) Biomarkers of canine glaucoma – early detection and disease progression

(Dr Andrew White, University of Sydney)

Glaucoma is a leading cause of blindness worldwide with the incidence in humans similar to rates reported in dogs. The pathophysiology of glaucoma is complex, multifactorial and incompletely understood. Progress in our understanding of the disease, its management and the prevention of progressive vision loss, has therefore been slow.

 The use of dogs over rodents as models of disease in ophthalmology has advantages including a larger eye that lends itself easily to surgical manipulation and a visual system that is adapted to vision in both day and night.  In order to determine whether dogs can be used as an effective model of disease of glaucoma in human patients, we must determine how to monitor disease progression and/or response to treatment objectively and determine similarities and differences between the species. We will investigate several clinically relevant potential biomarkers in canine glaucoma. A biomarker is a measurable anatomic, physiologic, biochemical, or molecular parameter indicative of a normal or pathologic process, disease state, or of a response to an intervention.  Biomarkers might include physiological measurements, blood tests, genetic, metabolic data, or measurements from images.  We will look to objectively measure disease progression and determine if and when glaucoma and its progression can be detected earlier and more accurately than it currently is. This will subsequently allow development of clinical trials and interventions targeted at a much earlier stage, with potential for greater effects, compared to what is achieved with current treatments. 

 

(5) Imaging and monitoring osteosarcoma with a novel radiolabelled peptide

(Assoc Prof Chiara Palmieri, University of Queensland)

Canine osteosarcoma is a common and aggressive bone cancer in dogs, with high mortality rate and less than 20% of affected patients surviving more than 2 years with standard therapy. The lack of specific and successful drugs and the prohibitive costs of treatment for the management of this tumour in dogs indicate the need for new diagnostic and therapeutic approaches. Cancer cells express many proteins that can be used as molecular targets. c-Met is a specific protein highly expressed in canine osteosarcoma and related to tumour growth and invasion. Developing a non-invasive and safe tool that could measure the expression levels of c-Met in real time would enable early diagnosis of canine osteosarcoma and facilitate the mechanisms to monitor the impact of treatment using new c-Met therapies. We will use a targeted diagnostic agent specific for c-Met to imaging and monitoring canine osteosarcoma in vivo. The key aims of this project will be the validation of this new imaging agent for osteosarcoma in dogs which will improve tumour monitoring (to identify residual cancer cells after therapy) and therapy selection (to identify patients who require further and/or different treatments).


Contact Details

Secretary: L Brodie Liaison Officer: J West
Melbourne, VIC, Australia
Email : [email protected] or [email protected]