Active Research Projects
| Dr. Emma van der Westhuizen | St. Vincent’s Institute of Medical Research | $145,000 over 2 years |
| “Enhancing microglial phagocytosis of toxic amyloid-beta peptides using small molecules” |
| Dr. Emma van der Westhuizen’s research focusses on an immune protein found on the surface of microglia that recognises sugar found in toxic protein deposits. People with Alzheimer’s disease (AD) have higher amounts of this protein and amyloid-beta proteins (Aß) in the brain than people without AD. The preliminary results of Dr. van der Westhuizen and colleagues suggest that strategies to remove or block this protein may lead to the development of effective AD medications. There are no small molecules targeting this protein currently in clinical trials and few labs working to develop these. The innovation consists of several new small molecules that target this protein which are more likely to breach the blood-brain-barrier than larger antibodies. Her team has 3D images showing some of their small molecules bind to the pocket with moderate strength. Funding provided by The Mason Foundation (managed by Equity Trustees) and NFMRI will be used to test these molecules in cell models of AD so that Dr. Emma van der Westhuizen and her team can translate them into pre-clinical animal models of AD |
| Prof. Isabelle Lucet | The Walter and Eliza Hall Institute of Medical Research | $171,106 over 2 years |
| “Targeting NEK7 mediated activation of the NLRP3 inflammasome as a new therapeutic avenue for Alzheimer’s disease” |
| Prof. Lucet’s innovative strategy is based on robust evidence linking inflammation in the brain to Alzheimer’s disease progression. Her team is particularly focused on the protein NLRP3, a key driver for the body’s first-line immune response and a highly sought after target in academia and the pharmaceutical industry worldwide due to its relevance to a wide range of diseases. They will aim to target the accessory key protein kinase, NEK7, through the development of small molecule drugs that render NEK7 unable to activate NLRP3, thereby reducing harmful brain inflammation in Alzheimer’s disease patients. Funding provided by The Mason Foundation (managed by Equity Trustees) and NFMRI will be used to create bespoke assays and develop tools and small molecule lead candidates that can be developed towards clinical trials. |
| Prof. Vito Ferro | The University of Queensland | $145,000 over 1.5 years |
| “Pharmacological chaperone therapy in a mouse model of MPS IIIA (Sanfilippo syndrome), a childhood dementia” |
| Sanfilippo syndrome is a rare genetic condition that causes childhood dementia – progressive, fatal brain damage in children with many features common with adult dementias. The median age of death reported is just 18 years and there is currently no effective treatment or cure. Prof. Ferro and his team have developed novel compounds called “chaperones” that can help support the stability and correct placement of the faulty enzyme present in Sanfilippo type A (MPS IIIA) patients. They have shown that their chaperones restore function of mutated enzyme and reduce the accumulation of waste products in cells from Sanfilippo type A patients. Funding provided by our anonymous partner and NFMRI will help support in vivo proof of concept studies. |
| A/Prof. James Wells | The University of Queensland | $344,610 over 2 years |
| “The development of Q2361 for skin cancer prevention and treatment in transplant patients” |
| Organ transplant patients require lifelong medication to prevent their bodies from rejecting their transplanted organs. Most patients receive a medication called tacrolimus. A side effect of this medication is a very high risk of a type of skin cancer called squamous cell carcinoma (SCC). These cancers develop on sun-exposed areas such as the face, grow aggressively, and lead to significant loss of life. There are currently no FDA-approved drugs for the treatment of SCC in these patients. A/Prof. Wells in collaboration with the Queensland Emory Drug Discovery Initiative (QEDDI), UniQuest’s commercial drug discovery arm, have identified and patented the compound Q-2361, which antagonises the effects of the tacrolimus medication in the skin. If given topically, Q-2361 allows the immune system to ‘switch on’ in the skin only and has enormous potential to combat skin cancer in transplant patients without needing to alter their medication and without leading to transplant rejection. Funding provided by NFMRI will help support scale-up chemistry and formulation development to advance this compound towards Phase I clinical trials. |
| Prof. Gursel Alici | University of Wollongong | $120,000 over 1 year |
| “Preclinical preparation for a novel multimodal human-machine-interface to enhance myoelectric control of transradial prosthetics hands” |
| This project aims to make preclinical preparations and optimize the developed prototype of a multimodal human-machine-interface for its application in the myoelectric control of transradial prosthetic hands. Current myoelectric control systems for prosthetic hand patients rely on unimodal bio-signals from surface electromyography (sEMG) sensors attached to a user’s residual stump. Prof. Alici and his team have developed a co-colated multimodal sensor that can acquire both sEMG and force myography signals from the same location of an arm, which significantly enriches the detected muscular information. Preliminary results demonstrate that their system outperforms conventional unimodal systems in multiple aspects, including robustness of user intention recognition, resilience of external noise, etc. Funding provided by NFMRI will help support prototype optimization studies to further advance the innovation towards clinical trial. |
| Dr. Hayley Bullen | The Burnet Institute | $150,000 over 1 year |
| “Developing novel antimalarials that prevent malaria parasites invading red blood cells” |
| As a novel approach to inhibiting parasite invasion, Dr. Bullen and her team have sought to target parasite enzymes responsible for folding invasion proteins. So far, they have identified 8 compounds which prevent parasite growth by inhibiting invasion of red blood cells. Importantly, they have found that these compounds are likely to have pan-species activity (ie. kill more than one species of malaria parasite). This is extremely important as prevalent malaria species vary across the world. Funding provided by NFMRI will help support pharmacokinetics optimisation studies conducted in collaboration with the Walter and Eliza Hall Institute of Medical Research. |
| Prof. Michael Rogers | Garvan Institute of Medical Research | $188,162 over 1.5 years |
| “Developing a lipid replacement to overcome a childhood autoinflammatory disease” |
| Mevalonate kinase deficiency (MKD) is a genetic autoinflammatory disorder with a spectrum of symptoms, including repeated flares of fever, joint pain, gut inflammation, severe abdominal pain, ulcers and skin rashes. The disease typically appears in early childhood and can be fatal in very severely affected individuals. This project brings together two collaborators with unique expertise in biochemistry and drug delivery, to develop a new treatment for MKD. Their approach is based on replenishing a crucial lipid metabolite that is lacking in MKD patients. The goal is to create an absorbable form of the missing metabolite that can be administered orally, in capsules or as a liquid suitable for children, thus bypassing the need for drug injection. Funding provided by our anonymous partner and NFMRI will help support preclinical development pathway studies for the lipid supplement as a simple, but innovative new treatment for MKD. |
| Prof. Bryce Vissel | St. Vincent’s Hospital Sydney | $293,328 over 2 years |
| “A novel therapeutic target to correct synapse loss and prevent cognitive decline in Alzheimer’s disease” |
| In Alzheimer’s disease (AD), the loss of connections made between brain cells (synapses) correlates more strongly with the emblematic cognitive decline associated with the condition, than does the accumulation of amyloid which consumes most research attention on AD. Treatments that directly target and attempt to rescue synapse loss represent an avenue by which we might most effectively treat cognitive decline. Prof. Prof. Bryce Vissel’s team seeks to target a mechanism involving abnormal synapse function by changing compositions of AMPA receptors (AMPARs), a key neurotransmitter receptor in the brain. Funding provided by The Mason Foundation (managed by Equity Trustees) and NFMRI will help support pre-clinical efficacy studies. |
| Prof. Kate Schroder | The University of Queensland | $250,000 over 1.5 years |
| Inflammasome proteins as novel drug targets for treating dementia |
| This project will aim to define the precise molecular mechanisms by which aggregated tau triggers inflammasome-dependent inflammation and neurodegeneration to validate exciting new drug targets for dementia. This project’s significance lies in its capacity to provide preclinical data to expedite human trials of Prof. Schroder’s emerging inflammasome inhibitors in AD and FTD. Given that the NLRP3 inhibitor Selnoflast is already in human trials for other diseases, there is potential for rapid research translation to meet urgent unmet need for people living with dementia. Funding from The Mason Foundation (managed by Equity Trustees) and NFMRI will help support validation studies for inflammasome proteins as novel drug targets for treating dementia. |
| Dr. Rebecca Nisbet | The Florey Institute of Medical Research | $152,450 over two years |
| “Vectorised antibody therapeutic targeting intracellular tau for the treatment of Alzheimer’s disease” |
| Over the last 10 years, Dr. Nisbet has led a research program aimed at developing novel tau antibodies as a therapy for Alzheimer’s disease. Together with her team, they have generated an antibody, RNJ1, that binds tightly to tau and prevents tau from clumping together. To enhance targeting of tau within brain cells, where tau is mostly localised, they engineered a small fragment of RNJ1 to create an intracellular antibody, also known as an intrabody. They have demonstrated that when the DNA of the RNJ1 intrabody, iRNJ1, is delivered to cells, the cells can effectively make iRNJ1, which is in turn able to bind to tau. To facilitate brain delivery, iRNJ1 DNA has been packaged into adeno-associated virus (AAV), a human virus that does not cause disease, but can effectively enter the brain and brain cells. Intravenous injection of mice with AAV-packaged iRNJ1 results in wide-spread brain delivery, as well as the successful generation of iRNJ1 in brain cells. Funding provided by The Mason Foundation (managed by Equity Trustees) and NFMRI will help support Dr. Nisbet and her team to conduct a large pre-clinical assessment of iRNJ1, including validation and safety studies. |
| Dr. Remy Robert | Monash University | $260,861 over 1.5 years |
| “Targeted killing of immunosuppressive regulatory T cells for the treatment of solid tumours” |
| Dr. Robert and his team have discovered a highly differentiated antibody with superior ability to eliminate tumour infiltrating regulatory T cells, with the potential to be further developed as a solid tumour treatment. The overall aim of the research program is to further differentiate and reposition the antibody program into a first-in-class antibody drug conjugate (ADC) program. The unique internalisation property of the antibody makes it amenable to an ADC approach. Furthermore, unlike the competitor program in development, an ADC approach doesn’t rely exclusively on the presence of patients’ immune cells for the elimination of the tumour infiltrating regulatory T cells. Funding provided by NFMRI will help support a preclinical proof-of-concept of an ADC approach. |
| Prof. Russell Dale | The University of Sydney | $137,324 over one year |
| “Brain RIBO-STRESS signature: a biomarker of neurodevelopmental and neuropsychiatric disorders” |
| Neurodevelopmental disorders affect 10% of children and include autism, ADHD, Tourette syndrome and schizophrenia – some of the biggest disorders of the developing brain. At present, treatment is supportive only, and there are no treatments that target ‘disease mechanisms’. There is increasing evidence that, in addition to genetic vulnerability, the expression of neurodevelopmental disorders is mediated by environmental factors that stress the body and brain (infections, trauma, stress, inflammation during pregnancy or early life). Using single cell RNA sequencing and proteomics, Professor Dale and his team have identified a biomarker signature in the blood of children with neurodevelopmental disorders that shows that their cells are stressed, and the immune system is not functioning normally. Funding provided by an anonymous partner and NFMRI will help support Professor Dale and his team to validate these findings in larger cohorts, which will in turn consolidate their intellectual property and commercial opportunities. |
| Dr. Pierre Qian | The University of Sydney | $180,000 over 1.5 years |
| “Mu Microwave catheter for treatment of hypertension” |
| Hypertension affects 1 in 3 adults and is the strongest modifiable risk factor for cardiovascular disease, yet only half of patients achieve target blood pressure control and up to 1 in 8 needs ≥3 medications. New antihypertensive therapies are urgently needed to address the growing cardiovascular disease burden. Renal nerve hyperactivity is a driver of hypertension. Renal denervation (RDN) using catheters placed into the renal artery to destroy with heat the surrounding nerves can reduce blood pressure. Conventional renal denervation systems use radiofrequency electrical current to generate heat but cannot be applied circumferentially around the artery and are too shallow to reach many of the renal nerves. Dr. Qian and his team at Westmead Hospital have invented the Mu Catheter, a microwave ablation system for renal denervation. Microwaves penetrate deeply into the fat around renal arteries circumferentially leading to effective denervation without causing significant arterial injury. Funding from NFMRI will help support the development of a proof-of-concept renal blood flow measuring device (and correlating dataset) that can continuously monitor renal blood flow to take advantage of this physiological endpoint to guide denervation therapy, thereby “unblinding” RDN and clarifying the value proposition of the Mu RDN system to investors. |
| Prof. Bernard Flynn | Monash University | $189,400 over one year |
| “Gastrointestinal-Restricted ALK5 Inhibitors for the Treatment of Intestinal Fibrosis” |
| Fibrosis refers to the accumulation of scar tissue in any tissue usually because of a sustained inflammatory insult. Approximately 30-50% of people with a diagnosis of inflammatory bowel disease (IBD), Crohn’s disease or ulcerative colitis, suffer from intestinal fibrosis. This intestinal fibrosis leads to strictures that obstruct the GI tract, requiring surgical intervention. Currently, there are no therapies available for the treatment of intestinal fibrosis and it remains a key unmet need in IBD treatment. Activin receptor-like kinase 5 (ALK5) is a key mediator of profibrotic signaling in the cell-types that drive fibrosis. Compounds that inhibit ALK5 have shown great promise in preclinical rodent models of intestinal fibrosis, but their clinical development has been curtailed by the adverse cardiovascular events that arise from inhibiting ALK5 in cardiac tissue. Prof Flynn (an expert in drug discovery and GI-directed therapeutics) and Prof Pitson (an expert in fibrosis cell biology) have developed a new class of GI-restricted ALK5 inhibitors (AKL5i) for the treatment of intestinal fibrosis. In this project, they will collaborate with the “third party” group of A/Prof Rimma Goldberg (IBD clinician researcher, Monash Health) and A/Prof Joshua Ooi (Centre for Inflammatory Disease, Monash Health), to achieve a proof-of-concept in rodent models of safety and efficacy. Funding provided by NFMRI will help support a preclinical proof-of-concept for a gastrointestinal restricted antifibrotic drug that inhibits known a biomolecular mediator of fibrosis, ALK5. |
| Prof. Michael Good AO | Griffith University | $50,000 over one year |
| “Dr. John Raftos AM Award” |
| Prof. Michael Good AO was granted the 2024 Dr. John Raftos AM Award in recognition of his achievements. The Award includes a $50,000 prize in the form of a research grant to support the researcher’s activities. The award will be used to part fund an ‘ELIspot’ reader, which is a machine that can enumerate immune cells that respond to certain antigens or immune stimulants. This is critical to Professor Good’s vaccine studies. It will be enormously labour-saving and be applicable to both the malaria and Streptococcal vaccine programs. Furthermore, the machine will be available to all Institute members. The Institute for Glycomics has agreed to contribute $69,300 towards the cost of the machine. |
| A/Prof Peter van Wijngaarden | Centre for Eye Research Australia | $50,000 over one year |
| “Dr. John Raftos AM Award” |
| A/Prof Peter van Wijngaarden was granted the 2024 Dr. John Raftos AM Award in recognition of his achievements. The Award includes a $50,000 prize in the form of a research grant to support the researcher’s activities. |
| Dr. Dorothy Wai | Monash University | $186,677 over two years |
| “Development of HsTX1[R14A], a novel therapeutic to reverse neuroinflammation in Alzheimer’s disease” |
| This project will advance the development of a novel drug candidate with the potential to reverse the memory deficits associated with Alzheimer’s disease (AD). AD is a debilitating disorder predicted to affect up to 1 million Australians by 2050, yet a cure for this disease remains elusive. Derived from a natural peptide from scorpion venom, HsTX1[R14A] targets a surface protein on brain immune cells that become overactive in AD. Blocking this protein reduces the activity of these cells and improves memory in a mouse model of AD. However, assessing the biodistribution and demonstrating that this peptide accesses the brain and is effective in a second mouse model of AD are key steps in progressing this novel drug candidate towards the clinic. Funding provided by The Mason Foundation (managed by Equity Trustees) and NFMRI will help support proof-of-concept studies for HsTX1[R14A] as a potential AD drug candidate and additional validation of the therapeutic value of targeting this specific pathway in AD. |
| Dr. Jenna Ziebell | University of Tasmania | $264,485 over three years |
| Alternate drivers of Alzheimer’s disease: Are microglia the problem? |
| Recent studies suggest microglia are highly associated with Alzheimer’s disease and could potentially be the initiators of disease. This research aims to understand if microglia are genetically programmed to drive Alzheimer’s disease (AD) progression. Dr Ziebell and her team’s innovative research plan will investigate whether transplanting microglia from “healthy” mice diminishes disease burden. Furthermore, they will examine whether transplanting microglia from “Alzheimer’s disease” mice changes neuropathology with ageing. This study design will investigate these factors in both biological sexes.This project is funded in partnership between The Mason Foundation (managed by Equity Trustees) and NFMRI. |
| Prof. Denise Doolan | James Cook University | $290,000 over two years |
| Development of a multi-antigen T-cell malaria vaccine |
| Despite the dramatic decline in mortality and morbidity during the past decade, there is now a resurgence of malaria. Vaccination with the current lead malaria vaccine candidate can induce partial protection, but efficacy is low (<35%) and short-lived. To address this need, Prof Doolan and her team have been pursuing an innovative approach to malaria vaccine development and together have identified four novel high-potential targets for a malaria vaccine to protect against all species of malaria. Each of these antigens can reduce liver-stage and blood-stage parasite burden against same-species and cross-species sporozoite challenge in mice, when administered in either of two vaccine regimens. Funding for this project will be used to enhance the pre-clinical package to support the translation of these lead antigens through the pre-clinical pipeline to phase 1/2a clinical testing, strengthen the IP portfolio, and attract a commercialization partner. |
| A/Prof Linda Wakim | Doherty Institute, The University of Melbourne | $145,000 over two years |
| A novel universal influenza virus vaccine that provides long-term protection against the flu |
| Vaccination remains the best way to prevent human influenza disease, a highly contagious and rapidly spreading acute respiratory disease. However, current influenza vaccines are sub-optimal relying on annual reformulation and delivery to the population to maintain protective immunity. Current vaccines also offer no protection during a pandemic outbreak, where the emergence of novel viruses from animal reservoirs spread rapidly worldwide, having a devastating impact on global health. This project unites A/Prof Linda Wakim, Prof Greg Qiao, Prof Bernd Rehm together with the WHO Collaborating Centre for Reference and Research and Influenza (CCRRI) to develop a novel “one-shot’ intranasal influenza vaccine that provides long term, cross strain protection against seasonal and newly emerging pandemic strains. Funding will be used to develop an improved vaccine formulation and perform key in-vitro and in-vivo pre-clinical testing. While the initial focus of this project is to develop an intranasal influenza virus vaccine, it is envisaged that the formulation will be developed with flexibility so that it can be easily and rapidly adapted to target other clinically relevant respiratory viruses (ie SARS-CoV-2). |
| Dr Livia Carvalho | Lions Eye Institute | $145,000 over two years |
| Investigating novel bile acid nanocapsules carrying neuroprotective agents for the treatment of retinitis pigmentosa |
| Retinitis pigmentosa is a rare, inherited degenerative eye disease that causes severe vision impairment. Dr Livia Carvalho and her team are developing a safe and effective nanocapsule system that can support sustained drug delivery into the eye for prolonged beneficial effects to help treat retinitis pigmentosa. Their preliminary research has shown that intravitreal administration into the eye of a neuroprotective drug can provide a transient protective effect in mouse models of inherited retinal diseases. In these animals, treatment was capable of reversing cell death temporarily in the first few days after treatment, but the effect was lost after a week. This project will establish a multidisciplinary collaboration between Dr Carvalho’s vision research lab and Dr Al-Salami’s bio-nanotechnology development lab to address this unmet need. Funding for this proof-of-principle project will be used to test the long-term treatment efficacy of this neuroprotective drug using a novel bile acid-based nanocapsule system compatible with direct eye delivery. |
| Dr. Prashant Bharadwaj | Edith Cowan University | $250,000 over two years |
| Analysis of neurofilament biomarkers for Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and childhood dementia |
| Currently, the diagnosis of Alzheimer’s disease (AD) is difficult, expensive, and there are no reliable biological indicators of the disease. Dr Bharadwaj and his team aim to develop a blood test for cognitive loss in AD by identifying a signature of the disease based upon specific proteins. The NFL protein has been shown to be a good indicator of many forms of neurodegeneration and not specific to AD only. Recent findings suggest the occurrence of distinct NFL variants in the brain and blood. Furthermore, NFL variants in AD blood appear to be different compared to healthy individuals. This project is a novel concept and aims to characterize these variants in different types of dementias. This funding will also support the use of mass spectrometry to help determine if specific variants are differently expressed in AD and identify whether these modifications form a signature unique for AD. If successful, findings from this study could ultimately improve the accuracy of AD diagnosis. This project is funded in partnership between The Mason Foundation (managed by Equity Trustees) and NFMRI. |
| Dr. Jonathan Danon | The University of Sydney | $143,904 over two years |
| Innovative molecules for imaging neuroinflammation in Alzheimer’s disease |
| Dr Danon and his team have recently developed a set of novel radiotracers designed to detect neuroinflammation with unprecedented sensitivity in humans of all genetic backgrounds. This grant will fund a crucial collaborative study that will be performed at the Centre for Advanced Imaging at the University of Queensland. They will validate the ability of these compounds to image neuroinflammation in preclinical animal models of Alzheimer’s disease using positron emission tomography (PET), generating data that will strengthen their IP position and take the innovation another step closer to preclinical first-in-human trials, commercialisation, and global distribution. These studies will be fundamental for translating their preliminary results into clinically useful tools that could help millions of people globally who live with Alzheimer’s disease. This project is funded in partnership between The Mason Foundation (managed by Equity Trustees) and NFMRI. |
| Prof. Ralph Martins AO | Edith Cowan University | $170,000 over two years |
| Specificity testing and cross-laboratory validation of a blood test for Alzheimer’s Disease |
| This research aims to accurately detect Alzheimer’s disease (AD) within a time-frame to allow positive lifestyle changes and ultimately therapeutic intervention. The work is based on the discovery that small vesicles, called exosomes, are released from cells acting as distinct indicators of the health status of the tissues from which they derive. Exosomes thus represent disease biomarkers. The novel hypothesis surrounding Dr Cheng’s research is that exosomes secreted from brain tissue migrate across the blood brain barrier into the blood where brain biomarkers are readily detected. This is equivalent to a ‘liquid biopsy’ of the brain reflecting neurological status. In preliminary studies she has already identified a panel of 16 serum exosomal miRNAs that are altered in AD compared to heathy patients. NFMRI funding will help validate the specificity of these potential AD biomarkers. Therapeutic strategies aimed at limiting neurodegeneration and improving quality of life in AD require methods to diagnose and monitor the disease in pre-clinical patients. Currently, definitive diagnosis of AD is only possible post-mortem or through PET neuroimaging that requires expensive equipment, highly trained operators and cerebrospinal fluid (CSF) collection. In comparison, blood is a conveniently collected, less-invasive source of biomarkers. Funding will enable this critical work to go full term and be translated to a reliable, economically viable, routine pre-clinical AD screen. This project is supported thanks to the generous funding provided by The Mason Foundation (managed by Equity Trustees). |
