2020 Funded Projects
Successful Grants for 2020
CONGRATULATIONS to the following researchers who have received funding from
the Canine Research Foundation for 2020
Investigating drug resistance in Australian canine heartworm infections
Prof Jan Slapeta - University of Sydney
Currently, canine heartworm disease affects hundreds of dogs in Australia every year, predominantly in far north Queensland. Thousands more dogs live with the threat of infection, with many owners using year-round preventatives to protect their dogs from acquiring this deadly disease. Spread by mosquitos, canine heartworm has a wide but poorly understood geographical distribution that appears to change over time. Currently, central and northern Queensland are experiencing high rates of infection, however, less than 20 years ago dirofilariasis also caused heartache for owners in coastal NSW including Sydney. The use of preventatives to stop infection is widespread among dog owners, with the Macrocyclic Lactones (MLs) drug family the mainstay of prevention. However, research from the USA is showing that drug resistance is emerging. The situation regarding drug resistance is currently unknown in Australia, although alleged cases of canine heartworm disease in dogs receiving preventatives suggest resistance might be present here. Our project aims to identify whether the single nucleotide polymorphisms (SNPs) associated with resistance are present in the canine heartworm population in Australia. We will do this by collecting microfilaria from infected dogs, prior to and post-application of MLs to determine if circulating microfilariae are cleared by the drugs. The information is essential, as the presence of resistance will have a significant impact on our ability to protect dogs in the future. We will empower Australian veterinary profession with knowledge on drug resistance, to enable monitoring the spread of drug resistance and identification of the driving forces behind disease re-emergence.
Assessment of BH3 Mimetics against canine haematological malignancies
Professor Caroline Mansfield - The University of Melbourne
The development of BH3 mimetics has revolutionised the treatment of Chronic Lymphocytic Leukemia (CLL) in people and is being investigated in other cancers including Non-Hodgkin’s lymphoma (NHL), acute leukemia and multiple myeloma. These drugs cause apoptosis (programmed cell death) in cancer cells by binding and inhibiting the antiapoptotic protein BCL2. Venetoclax is a BH3 mimetic that has recently been approved for the treatment of CLL and acute myeloid leukemia in people and has greatly improved survival times in these diseases, which are known to overexpress BCL2. Hematological cancers including CLL, NHL, multiple myeloma, and acute leukaemia are common in dogs, representing more than 25% of all cancers. Increased BCL2 concentrations occur in dogs with NHL and may also occur following exposure to chemotherapy and prednisolone. Therefore, BH3 mimetics may be an option for treatment of this cancer. The expression of BCL2 has not been evaluated in other haematological malignancies in dogs and the effect of BH3 mimetics in treating cancer in dogs has not been evaluated from dog-derived case samples. Our primary aim is to assess the sensitivity of cancer cells from dogs with haematological malignancies to BH3 mimetics in vitro. Our second aim is to measure expression of apoptotic proteins in dogs with hematological cancers compared to normal dogs, and dogs with diseases other than cancer that are receiving prednisolone. This study will provide initial information in determining whether BH3 mimetics may be rational treatments for dogs with hematological cancer.
Phage therapy for antibiotic-resistant Staphylococcus pseudintermedius in canines
Associate Professor Karla Helbig - La Trobe University
Staphylococcus pseudintermedius is the causative pathogen of canine pyoderma, the most common chronic skin infection seen within the veterinary sector. Alongside this, S. pseudintermedius is also associated with severe infections occurring within the reproductive, respiratory and urinary tract of dogs. Previous studies have identified that up to 60% of dogs are infected with methicillin-resistant S. pseudintermedius (MRSP), which are able to survive applications of antibiotics, the current frontline medication used to treat all bacterial infections. With an evident increase in antibiotic resistance and a parallel decline in effective treatment options, there is an urgent requirement for novel therapeutics. To address the demand for treatment options for canine S. pseudintermedius infections, our project focuses on bacteriophages (phages), which are small viruses that specifically infect and kill bacteria of interest. To date, we have isolated four novel phages that successfully lyse multiple strains of S. pseudintermedius isolated from the skin, ear, urinary, reproductive and respiratory tract from infected dogs. We have also developed and optimised an in vivo silkworm model for the rapid safety and efficacy testing of our phages, prior to their use in animals. This study will further optimise the development of our novel phages able to kill S. pseudintermedius into creams to treat topical canine pyoderma infections, or intravenous solutions for the treatment of systemic infections in the urinary, reproductive and respiratory tract. Promising results from this study will facilitate clinical trials of phage therapy in dogs, to advance phage therapy as an alternative to antibiotics.
Mass spectrometry based blood plasma prostanoids quantification in dogs
Professor Paul Mills - University of Queensland
Pain in dogs can be difficult to assess. Dogs can obscure pain or have a high tolerance to pain and may show no signs of pain despite suffering. Objective methods to assess pain are therefore required. There are no biomarkers established to study pain and inflammation in dogs. The conventional methods of accessing pain and inflammation are by studying behavioural changes, measuring cortisol, acute phase proteins and prostaglandins using ELISAs or RIAs. But these assays are time consuming, antibody and species specific, so expensive and prone to false results. Specific biomarkers of pain and inflammation would permit better understanding of disease and response to therapeutics. In addition to biomarkers, measuring the responses of inflammatory mediators, particularly the prostanoids, would be useful, since they are the direct target of the non-steroidal anti-inflammatory drugs (NSAIDs), such as ketoprofen and carprofen. Inflammatory mediators like prostaglandins and other prostanoids are released in to systemic circulation in clinical conditions osteoarthritis, cancer and muscular dystrophy. Measuring these mediators can be an option to study pain and inflammation, early detection of diseases, and also helps to study the efficacy of analgesics. Modem mass spectrometry-based biomarker discovery is gaining popularity in veterinary medicine for being specific, sensitive and label free techniques. Studying inflammatory mediators have always proven to be an important diagnostic tool in testing the efficacy ofNSAIDs, cancer biology and chronic inflammatory disease conditions. Currently, there are no objective measurement ofprostanoids in dog plasma. The current study proposes to develop a panel of lipid mediators of tissue damage, to objectively assess pain and inflammation following surgery in dogs and the response to analgesics. The developed analytical method for quantifying prostanoids can also aid in studying diagnosis and prognosis of other inflammatory disease conditions.
Contact Details
Secretary: L Brodie Liaison Officer:Melbourne, VIC, Australia
Email : [email protected]