NOVEL THERAPIES FOR ALZHEIMER'S DISEASE BASED ON A-BETA - METAL INTERACTIONS
Funder
National Health and Medical Research Council
Funding Amount
$461,443.00
Summary
The genetic data clearly show that the amyloid protein (A-beta) is central to the brain damage which occurs in Alzheimer's disease (AD). However exogenous or environmental factors involved in regulating its toxic actions are not understood. We have shown that the metals zinc and copper have dramatic effects on the properties of A-beta and that chemicals which alter the amounts of these metals in the brain may be useful in treating the disease. In this project we are investigating the ability of ....The genetic data clearly show that the amyloid protein (A-beta) is central to the brain damage which occurs in Alzheimer's disease (AD). However exogenous or environmental factors involved in regulating its toxic actions are not understood. We have shown that the metals zinc and copper have dramatic effects on the properties of A-beta and that chemicals which alter the amounts of these metals in the brain may be useful in treating the disease. In this project we are investigating the ability of one such compound to affect the metabolism of A-beta in a mouse model of AD.Read moreRead less
Development Of Iron Chelators For The Treatment Of Friedreichs Ataxia And The Role Of Frataxin In Iron Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$550,987.00
Summary
Friedreich's ataxia (FA) is a neuro- and cardio-degenerative disease where there is an accumulation of toxic Fe in the mitochondrion. Excitingly, work from our current NHMRC grant showed iron plays a significant role in FA pathology. Importantly, we developed new drugs (Fe chelators) which rescue the cardiac pathology of FA in an animal model. Studies will now assess if our drugs prevent the neurodegeneration of FA in another animal model. This work could lead to novel therapies for FA.
Next-generation Glioblastoma Multiforme Therapies Based On Multistage Delivery Nanovectors
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Nanomedicine provides novel therapies with enhanced treatment success and reduced side effects, which improve the patient’s quality of life. Drug delivery systems that are able to treat highly drug-resistant tumours such as glioblastoma multiforme (GBM) are a key target for nanomedicine-based therapies. We will investigate a new GBM treatment by developing a multistage delivery nanovector to selectively carry and release a combination of chemical and physical therapeutics.
Preclinical Development Of A Therapeutic Anticancer Antibody To C-Met
Funder
National Health and Medical Research Council
Funding Amount
$435,530.00
Summary
Many common cancers cannot be effectively treated. A range of these cancers (e.g. gastric and lung cancer) display the molecule c-Met on their cell surface. c-Met promotes tumour growth; therefore, blocking c-Met is a promising strategy for treating these cancers. However, no antibodies or drugs that target c-Met have been licensed. The therapeutics that are being developed to target c-Met all have considerable limitations. Thus, there is an opportunity to develop a 'best-in-class' therapeutic.
Therapeutic Targeting Of MYCN Oncoprotein Stability In Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$590,206.00
Summary
A high level of MYCN protein is a major indicator of aggressive neuroblastoma (NB) but unfortunately there have been many barriers to the design of targeted therapies. We have identified a protein called PA2G4 which is a cofactor for MYCN in promoting cancer cell growth. We have developed a compound which inhibits PA2G4 and MYCN protein levels and reduces tumour growth. We will examine how PA2G4 cause aggressive tumour characteristics and test new methods to block PA2G4.
Antibiotic Potentiators As An Alternative Therapeutic Option For The Treatment Of Extensively Drug-resistant Gram-negative Infections
Funder
National Health and Medical Research Council
Funding Amount
$856,858.00
Summary
Antibiotic mono-therapies are increasingly ineffective for hard-to-treat bacterial infections, forcing clinicians to rely on combinations of antibiotics. Our project has identified compounds that have weak to no antimicrobial potency in their own right, yet when combined with an existing antibiotic they potentiate its activity and restore its ability to treat resistant infections. These antibiotic potentiators are exciting alternatives to current therapies with reduced risk of induced resistance
Treatments that target cancer causing genes called oncogenes have resulted in new treatment paradigms for cancer. We suggest that outcomes of patients with cancer will be further substantially improved by understanding how cancers can overcome resistance to these treatments that develops in many patients. To accelerate the adoption of these and other new treatments for cancer we will also develop new frameworks for clinical trials.
There is an unmet medical need to develop new therapies that are safer and potentially allow the treatment of a broader range of cancers. Inhibiting the immune checkpoints TIGIT and CD96 represents an opportunity that may parallel and indeed complement the activity and impact of other lymphocyte checkpoint inhibitors in human cancer (eg. PD1/PD-L1). While testing these as targets in mice we will also learn more about their ligand CD155 and their expression in human tumors.