Over the last 30 years, the Foundation has supported by way of grants a diverse range of medical research projects. These have included:
Prof Michael Good AO, Griffith University, “Manufacture and evaluation of a chemically attenuated Plasmodium falciparum whole parasite blood-stage malaria vaccine”, $200,000 over one year (2018)
Prof Good’s team has developed and patented a novel approach to a malaria vaccine that in their published pre-clinical studies has shown long-lasting protection against different strains and species of the malaria parasite. This approach is based on the use of the entire parasite which is made non-infectious by treatment with a chemical agent. For the human malaria parasite (Plasmodium falciparum) vaccine manufacture involves in vitro culture of the malaria parasite followed by chemical treatment. This has since been administered as a single dose to eight volunteers who all developed strong cellular immune responses. Since the vaccine has been shown to be safe and well-tolerated, Prof Good’s team now plans to undertake a Phase Ib trial, which will involve 36 volunteers and test the efficacy of the vaccine. NFMRI funding would help support the vaccine manufacture for this trial. The associated clinical trial and activities are already funded via other sources, including Rotary.
Prof Philip Sutton, Murdoch Children’s Research Institute, “Vaccinating against Helicobacter pylori-induced gastric cancer”, $150,000 over one year (2018)
A/Prof Sutton has invented a vaccine that can prevent gastritis in mice. His vaccine targets the enzyme produced by H.pylori, which opens up gaps in the normally tight, impermeable barrier of the stomach lining. A/Prof Sutton believes that by preventing disruption of this barrier, either before or after H.pylori infection, that they may completely prevent the development of gastritis. A/Prof Sutton wishes to test this vaccine in clinical trials, but to do so he needs to optimise the manufacturing process of the vaccine antigen in order to be able to produce the antigen in sufficient quantity and quality for taking into clinical trials. NFMRI funding will help support optimisation of the manufacturing process for the vaccine antigen. Luinabio, one of the most experienced company in Australia for producing recombinant vaccine antigens used in clinical trials would be contracted by A/Prof Sutton to carry out this work.
Dr Joanna Woodcock, The University of South Australia, “Pre-clinical evaluation of 14-3-3 protein inhibitors for lung cancer therapy”, $50,002 over one year (2018)
The cellular protein, 14-3-3, is abundant in many cancers including lung cancer and the increased amount of 14-3-3 protein above normal levels strongly equates to the severity of the cancer and poor patient survival. Importantly, in experimental systems, reduction in levels of 14-3-3 protein in lung cancer cells has been shown to block cancer cell growth and cause cell death. Therefore, 14-3-3 protein represents a promising ‘molecular target’ for the development of new anti-cancer treatment for lung cancer. Several other laboratories in the world have attempted to generate drugs to interfere with14-3-3, but without much success. Through Dr Woodcock’s research, they have found a novel way to inactivate 14-3-3 protein which already shows greater promise. Based on their knowledge of 14-3-3 protein structure and function, they have identified chemical compounds that selectively inactivate 14-3-3 and have shown that these compounds kill lung cancer cells and reduce lung cancer tumour growth in an animal model. They are currently evaluating these compounds in more relevant models of human lung cancer to assess the potential of our 14-3-3-targeting compounds as anti-cancer drugs for lung cancer. This project is supported thanks to generous funding from the NSW Community Foundation, the NSW Community Foundation – Nicholas and Phyllis Pinter Trust (both are managed by Equity Trustees) and NFMRI. Our combined funding will help support the assessment of pharmacokinetic properties of the drug compounds by scientists at CDCO and analysis of those compounds’ properties using RPPA. These studies will enable Dr Woodwock to fully assess the drug-like properties of those compounds and their potential efficacy for lung cancer.
Prof Eric Gowans, The University of Adelaide, “A DNA Vaccine for Zika Virus”, $293,880 over three years (2016 – 2018)
The Gowans laboratory has developed a novel DNA vaccine that is more effective than canonical DNA vaccines and elicits robust immune responses in small (mice) and large (pigs) animals. A vaccine for the Zika virus is urgently required because there is no therapy, and the link with microcephaly in children born to mothers who were infected during pregnancy demands that women of child-bearing potential be immunised. As canonical vaccines (eg. live attenuated vaccines) require a considerable period of development, a DNA vaccine that can be generated in a matter of weeks represents an attractive alternative.In this proposal, Prof. Gowans’ team examine the efficacy of novel DNA vaccines designed to elicit cell-mediated immunity to the Zika virus non-structural proteins or Zika neutralizing antibody in mice. Thus, a major component of the project is to examine the immune responses in mice and pigs, and the protective efficacy of the vaccines in mice, with a view to identifying the most appropriate strategy to further develop for follow up studies in human clinical trials.This project is supported thanks to generous support from the NSW Department of Primary Industries.
Prof Des Richardson, The University of Sydney, “Commercial translation of innovative null hepcidin analogues that prevent the anaemia of chronic disease (ACD)”, $105,500 over two years (2017-2018)
The anaemia of chronic disease (ACD) is a severe cause of morbidity and mortality in many millions of patients with cancer or inflammatory diseases and is due to excessive levels of the hormone hepcidin. These diseases induce excessive levels of hepcidin, which in turn promotes iron storage, thus preventing its release into the blood leading to severe and debilitating anaemia. Prof Richardson has discovered that hepcidin is bound in the blood by a specific protein and has since developed an analogue that leads to urinary excretions of excessive hepcidin. NFMRI support will enable commercialisation of this optimal analogue.
Dr Nicholas Opie, The University of Melbourne, “Safety validation of the stent rode: a biomedical device for paralysis that converts thoughts into computer commands”, $390,000 over two years (2017-2018)
Dr Opie has developed a minimally invasive brain machine interface that has the potential to return mobility and independence to people with paralysis. His technology can record brain signals and convert them into useful commands that can be used to control computers, wheelchairs, exoskeletons and/or prosthetic limbs. Translation of existing brain machines is hampered by invasive surgical procedures, which require access the brain and lead to immune reactions that are causing device failure within months. Dr Opie and his team have already done enormous progress since receiving a $1.3m seed funding grant from the Defence Advanced Research Projects Agency – having already developed an implantable stent-electrode array that can record neural information from within a blood vessel, mitigating risks associated with open brain surgery. NFMRI support will help them translate this research into clinical translation via the conduction of a world-first human trial in 2018. To meet this milestone, they must first manufacture the technology in an FDA approved and ISO certified facility and conduct the necessary preclinical experiments to demonstrate reliability, efficacy and safety.
A/Prof Michelle Hill, QIMR Berghofer, “Blood glycoprotein panel for early detection of oesophageal cancer”, $169,204 (1 year, 2017)
A/Prof Hill’s research aims to transform the detection and management of oesophageal adenocarcinoma (OAC) by developing a blood test. OAC is increasingly common due to growth of the major risk factors: chronic reflux and obesity. Although effective treatments are available for early OAC, outcomes remain poor because most cases are diagnosed at advanced stages due to the lack of practical and effective screening tools. A/Prof Hill has identified and patented a panel of readily translatable glycoprotein biomarkers, which can differentiate OAC from benign conditions and healthy controls. Her research program is in the process of evaluating these markers in large patient samples, as a step toward development of a diagnostic test that can be introduced into clinical practice. NFMRI support helped develop one embodiment of the innovation, the clinical immunoassay. Working with industry partner Precision Antibody, they aimed to generate monoclonal antibodies that recognise the three best biomarkers for use to generate immuno-assays. Successful completion will enable the development of a practical diagnostic test based on our biomarkers.
Prof Stephen Haswell, Deakin University, Advanced zoonotic disease detection through lab-on-a-chip technology, $372,000 (3 years, 2015-2017)
Funded through a partnership between the NFMRI and the NSW Department of Primary Industries, Prof Haswell’s project focuses on the design, manufacture and commercialization of a cost-effective lab-on-a-chip device that can rapidly identify the presence of infection and the causative virus from a range of existing possibilities. The device, which will cost less than $20, will take less than an hour to generate results and will be able to be linked wirelessly to a database to produce a range of control and treatment options, including vaccine-specific selections, where appropriate.
Prof Michael Good AO, Griffith University, Producing and testing a GMP grade peptide conjugate vaccine to prevent infection with group A streptococcus, $251,000 (3 years, 2015-2017)
Following an impressive 20 years of work on the development of a vaccine developed to prevent infection with group A streptococcus – the causative agent of tonsillitis, deep tissue septis, pyoderma and rheumatic heart disease – this project will focus on producing, at clinical grade, a novel GMP grade peptide conjugate vaccine for a Phase 1 trial.
Professor Mark Smythe, The development of human Hematopoietic Prostaglandin D2 Synthase Inhibitors (HPGD2S) for allergic asthma, $80,078 (1 year, 2016)
Professor Smythe’s research team is pursuing new and innovative asthma therapies by targeting a different and specific enzyme, HPGD2S, involved in the inflammatory mechanisms of asthma. His team has developed and optimised a series of potent and specific inhibitors of HPGD2S that are orally bioavailable and efficacious in in vivo animal models. NFMRI’s support will provide access to additional research studies and facilities to profile the compounds on human bronchial epithelial cells in order to study respiratory function. These studies will aid in the selection of drug candidates, which will provide efficacious treatment for the cause, not symptoms, of asthma. The funding in particular will provide access to external collaborator Asterand Bioscience in order to accelerate the identification and validation of their drug candidates.
Dr Tim Molloy, miR-127a as a biomarker and druggable target for radiotherapy resistance in breast cancer, $126,000 (3 years, 2014-2016)
Radiotherapy is an essential component of treatment for almost all breast cancer patients, and confers a profound benefit to patient survival. However, the presence of radiotherapy-resistant cells within the tumours of a significant minority of patients can lead to treatment failure resulting in relapse and death. Additionally, there are currently no biomarkers in clinical use which can identify resistant tumours to allow the proper tailoring of radiotherapy treatments to individual patients. Our group seeks to identify and characterise “microRNA” master regulators which control the processes of radiotherapy resistance in breast cancer. In preliminary work we identified a novel microRNA, called miR-1274a, which when at high levels in breast cancer cells significantly increases their resistance to radiotherapy. In the current study we aim to further investigate miR-1274a. We hypothesize that the miRNA itself or the genes that it regulates may be valuable biomarkers of radiotherapy resistance, and therefore could form the basis of diagnostic tests which may be useful in the clinic. In addition, we hypothesize that by treating radioresistant breast tumours with synthetic miR-1274a inhibitors in vivo, we can re-sensitise them to radiotherapy, thereby improving the efficacy of this vital treatment in otherwise recalcitrant tumours.
A/Prof Lenka Munoz, The University of Sydney, Improving chemotherapy response rates in brain cancer, $396,103.50 (4 years 2013-2016)
In a search for ways to limit the spread and to stop lethal recurrence of brain cancer, Dr Munoz’ research focuses on the inflammation caused by the tumour as a key to brain cancer progression. This research has found that cells surrounded with inflammation appear to move further because the inflammation makes it easier for tumour cells to propel themselves through tissue. The more inflammation in the proximity of a tumour cell, the faster glioblastoma cells travel. This project will make this the first group to report that drugs turning off the activity of an inflammatory protein called MK2 are effective in blocking inflammation in brain tumours. Blocking inflammation may prevent the invasive spread of cancer cells into healthy brain tissue, thus preventing the formation of novel tumours and potentially improving patient’s response to temozolomide (Temodal) during chemotherapy.
A/Prof Janet Davies, Queensland University of Technology, Towards an improved allergen immunotherapy vaccine targeting subtropical grass pollens, $100,000 (2 years, 2015-2016)
Grass pollen allergens are a major cause of hayfever and allergic asthma worldwide. Treatment by grass pollen immnotherapy vaccines improves patients’ symptoms, quality of life and productivity. Importantly, such therapy can reduce the burden of asthma. However, most vaccines are based on pollens of temperate rather than subtropical grasses. Optimised vaccines based on subtropical grass pollens are needed to provide more specific and effective allergen desensitisation treatment for patients in subtropical regions. Here we aim to utilise our intellectual property and know how pertaining to subtropical grass pollen allergens to develop a new method to measure and standardise the allergen content of subtropical grass pollen allergy vaccine products. The outcomes will have the potential to meet the growing need of patients in subtropical regions of Australia, Asia, Africa and America. An additional utility for this novel method is in outdoor allergen monitoring.
Dr Sanjaya Kuruppu, Monash University, A Potential New Treatment for Alzheimer’s Disease from a Snake Venom, $90,000 (1 year, 2016)
The project outlined in this application relates to a novel molecule that we have discovered from the venom of a snake. We have made a synthetic version of this molecule and have conducted an extensive array of in vitro studies. Our current data look very promising, and indicate that this molecule targets two enzymes that play a key role in the initiation and progression of Alzheimer’s disease. We believe that this molecule will serve as a template for the development of a whole new class of compounds that could be used in the fight against Alzheimer’s disease. However the in vivo efficacy of the compound we have developed must first be determined. In the studies outlined here-in we will test this molecule in a mouse model of Alzheimer’s disease. Our laboratory currently lacks the technical expertise to conduct these in vivo studies. Therefore we will collaborate with the laboratory of Prof David Small (Menzies Research Institute, University of Tasmania) who is a leading expert in the field of Alzheimer’s disease research.
A/Prof Bernard Flynn, Monash University, Sphingolipid targeting agents in the treatment of cardiac fibrosis, $100,000 (1 year, 2016)
The particular focus of this application, cardiac fibrosis, is the lead cause of heart failure and a major cause of death in the western world. This collaborative research group has drawn together experts in cardiac fibrosis, cell signalling pathways, enzyme assays, medicinal chemistry and metabolomics to help identify a suitable biomolecular target for fibrosis and to design drug molecules to inhibit this target. The focus has been on a class of lipid signalling molecules called sphingolipids, which control cell functions particularly during infection, inflammation and wound healing. Support from NFMRI will enable A/Prof Flynn to access both internal collaborators such as the Monash Centre for Drug Candidate Optimisation and external collaborators such vivoPharm to assist with targeted studies.
Dr Andrew Mitchell, The University of Sydney, Towards new treatments for bacterial meningitis, $28,892 (1 year, 2015)
Dr Andrew Mitchell, a young researcher from the University of Sydney, has identified a previously unknown cell type that drives inflammation. The results of his study will form the foundation for developing innovative new therapies for bacterial meningitis.
Prof Nicholas Shackel, The University of Sydney, Biomarker research for liver cancer, $225,500 (3 years, 2013-2015)
This research will develop new clinical tests in liver cancer, which will impact on diagnosis and determine outcomes using new genomic technologies. The research is novel and will lead to the development of personalised genomic medicine in which an individual can be uniquely assessed for the likelihood of developing liver cancer, enhance diagnosis, determine the risk of cancer spread and responses to treatment.
Emeritus Prof John McAvoy, Save Sight Institute, Chair in experimental ophthalmology, $3,669,902 (15 years, 2001-2015)
With approximately 20 million people affected, cataract is the most common cause of blindness in the world today. Currently, the most effective treatment for cataract is surgery, which involves removal of opaque cellular material and insertion of a plastic intraocular lens into the remaining capsular bag. Although initially effective in restoring sight, a complication of surgery is the development of a secondary cataract. A major focus of this research has been to identify ways of maintaining the normal lens cell phenotypes and provide conditions that promote regeneration of normal lens structure and function. To achieve this goal, greater understanding is required on the factors that maintain epithelial cells and promote their growth and differentiation into the highly elongated and oriented/aligned fibres that determine lens optical properties. In other words, the team needs to find out how to recapitulate normal developmental processes in order to successfully regenerate lenses after cataract surgery.
A/Prof Wendy Cooper, Royal Prince Alfred Hospital, Personalised medicine in lung cancer, $95,000 (2 years, 2014-2015)
There is a revolution underway in cancer management whereby treatment is ‘personalised’ to the genetic changes in each person’s cancer. This promises to maximize the benefit of specific treatments and reduce harmful side effects. A key part of this process is finding biomarkers that predict response to particular treatments. The aim of this research project is to identify biomarkers in lung cancer and mesothelioma that can be used to help select the best treatment for every individual patient. The team is investigating abnormal expression of protein and amplification of genes in lung cancer and mesothelioma that can potentially determine how well a patient will respond to treatment or how quickly or slowly their disease is likely to progress. This research has provided new diagnostic capability at Royal Prince Alfred Hospital and is now scaling up to assist more patients in need.
A/Prof Max Conway,The University of Sydney , Research into ocular melanoma, $215,000 (5 years, 2010-2014)
Eye melanoma is the most common primary intraocular cancer in humans. Up to 60% of patients die due to secondary spread many years after the primary cancer is removed surgically. There is currently no effective treatment for metastatic disease. Recently, a promising new class of anticancer drugs (Histone Deacetylase inhibitors or HDACi that are less toxic than conventional therapies, but can enhance their activity) have been identified. These novel, non-toxic agents may have the potential to improve the management of eye melanoma.This project aims to examine the potential for these agents to be used in eye melanoma sufferers.
A/Prof Michael Buckland, Brain and Mind Research Institute, Molecular changes in gliomas, $270,000 (3 years, 2012-2014)
Gliomas are the most common type of brain cancer and cause many deaths in Australia every year. In order to design effective strategies for the treatment and detection of glioma, it is important to understand the underlying genetic mutations, which lead to disease. Recent studies have found that the isocitrate dehydrogenase (IDH) gene is mutated in 70-80% of some glioma subtypes, suggesting it may be an early mutation that plays an important role in the development of brain cancer. It is thought that IDH mutations may contribute to cancer by changing patterns of methylcytosine and hydroxymethylcytosine on DNA, thereby changing gene expression to favour cancer development. This study aims to validate this theory by investigating how patterns of methylation and hydroxymethylation change in gliomas, and whether they differ between gliomas with and without IDH mutation.
A/Prof Michele Madigan, Save Sight Institute, Dry age-related macular degeneration, $180,000 (3 years, 2012-2014)
This research project is directed towards improving understanding of the role of the immune system in normal ageing of the eye and age-related macular degeneration (AMD). This information will also be useful for identifying potential therapeutic targets relevant to AMD patients.
A/Prof Wendy Cooper, Royal Prince Alfred Hospital, Personalise medicine for lung cancer and mesothelioma, $125,000 (2 years, 2012-2013)
There is a revolution underway in cancer management whereby treatment is “personalised” to the genetic changes in each person’s cancer. This promises to maximise benefit of specific treatments and reduce harmful side effects. A key part of this process is finding biomarkers that predict response to particular treatments. The aim of our research project is to identify biomarkers in lung cancer and mesothelioma that can be used to help select the best treatment for every individual patient.
A/Prof Sasha Klistorner, Save Sight Institute, Multifocal visual evoked potentials in optic neuropathies: understanding the mechanism of axonal loss in optic neuritis and enhancing early detection of glaucoma, $903,531 (10 years, 2004-2013)
Save Sight Institute recently reported the first successful simultaneous binocular recording of a VEP from multiple points in the visual field, and established that it could be used to detect blind spots objectively. It has now established a potentially major advance in detecting functional loss by utilising the phenomenon of binocular interaction as a means of enhancing early defects. This study will explore this concept extensively and lead to a better understanding of the pathophysiology of early glaucomatous damage by comparing subjective thresholds, objective functional signals monocularly and binocularly, with structural changes all in the same individual. The technique will aid in the diagnosis and management of glaucoma – a disease that currently is one of the 3 most common causes of blindness in the western world. Earlier diagnosis of glaucoma and/or earlier detection of progression would enable earlier institution of appropriate therapy to help preserve vision among our elderly, and would be another step toward reducing the burden of glaucoma-related morbidity in the world.
Prof David Ma, St Vincent’s Centre for Applied Medical Research, Role of MicroRNAs as regulators of cell survival and differentiation in acute myeloid leukaemia, $292,500 (3 years, 2011-2013)
Acute Myeloid Leukaemia (AML) is a cancer of the blood. It is caused by the accumulation of genetic abnormalities leading to uncontrolled cell growth, bone marrow failure and death. While unique gene defects have been discovered in some AML types, the cause of the leukaemic transformation remains unknown in a significant proportion of cases. This shortcoming in understanding AML hampers the ability to cure the disease. Abnormal alterations in small regulatory genes called microRNAs have recently been shown to be involved in the development of many cancers. Studies using gene chip technology have uncovered previously unknown abnormalities in microRNAs in unique subtypes of AML. In this study, the research team postulated that microRNAs contribute to the development of subtypes of AML in two ways: by enhancing cell survival and preventing blood cells from reaching maturity. The new knowledge generated by this research will lead to a better understanding of the biology of this rapidly fatal cancer. This may aid in the invention of diagnostic tests and target specific drugs, thus improving patient survival.
Prof Douglas Joshua and Dr Ross Brown, Royal Prince Alfred Hospital, The inhibitors of immune effectors in multiple myeloma, $240,000 (3 years, 2011-2013
Tumour cells should be removed and destroyed by the body’s own defence mechanisms in a similar way that viruses and bacteria are removed. However, the tumour cells themselves upset this normal process and so the normal process of so-called immune control is destroyed, or at least suppressed. Prof Joshua and Dr Brown have been trying to identify how this suppression works and to identify ways to allow the normal anti-tumour immune control to be restored. This work has identified several important new mechanisms and has in several cases identified how to correct the deficiencies.
Other grants include:
- Early treatment of AIDS
- Cancer of the prostate
- Malignant tumors of the eye, focusing on childhood
- The growth of malignant tissue cells outside the body and developing methods of modifying the activity of those cells without damaging normal cells
- The mode of development of the lens of the eye and formation of cataracts
- The relationship between some cancers and viruses
- The early electronic diagnosis of glaucoma and the accurate monitoring of progress, reducing the risk of blindness
- The accurate definition and tracking of nerve fibres from the eye to the brain and the influence of those fibres on the interpretation, by the brain, of the visual signals
- Funding the internet enablement of the South Eastern Sydney Illawarra Health’s Service’s electronic medical library
- Prevention of bony Metastases in Prostate and Breast cancers
- Chemical induced Neurotoxicity in Cancer treatment
- Vascular growth and tumour invasion in retinoblastoma and ureal melanoma
- Research fellowship at the Save Sigh Institute, Sydney Hospital
- Molecular profiling re myeloid leukaemia
- Gene expression profiling of lymphoma
- Restoration of pathology specimens, Pathology Museum
- Winston Library: purchase of medical research books