The Effect Of Selected Nutraceuticals On Brain Blood Vessels And Memory.
Funder
National Health and Medical Research Council
Funding Amount
$445,206.00
Summary
The human brain receives 1000L of blood per day, distributed through minute vessels called capillaries. The integrity and function of brain capillaries is compromised with aging and this may contribute to memory disturbances. Our laboratory has identified several naturally occurring compounds that prevent age-associated defects of brain capillaries. The primary aim of this project is to explore if these agents are beneficial for restoring brain capillary function and memory.
Therapeutic Induction Of Dytrophin-positive Revertant Fibres In The Mdx Mouse
Funder
National Health and Medical Research Council
Funding Amount
$454,825.00
Summary
Revertant fibres are low-abundance, dystrophin-positive fibres found in muscle of DMD patients and animal models. These fibres appear to have a selective advantage over dystrophin negative fibres, as they accumulate with age. Characterisation of dystrophin mRNA has identified in-frame transcripts missing multiple exons, which either exclude a nonsense mutation or restore the reading frame around a deletion. We have designed antisense oligonucleotides (AOs) to bind regions flanking the exon conta ....Revertant fibres are low-abundance, dystrophin-positive fibres found in muscle of DMD patients and animal models. These fibres appear to have a selective advantage over dystrophin negative fibres, as they accumulate with age. Characterisation of dystrophin mRNA has identified in-frame transcripts missing multiple exons, which either exclude a nonsense mutation or restore the reading frame around a deletion. We have designed antisense oligonucleotides (AOs) to bind regions flanking the exon containing the dystrophin mutation in the mdx mouse. The AOs interfere with processing of the pre-mRNA to exclude the mutation and allow a slightly shortened dystrophin to be synthesised. The use of AOs to modify RNA processing allows the gene to function under the control of natural regulatory elements. We have shown that AOs can induce dystrophin expression and improve strength in dystrophic (mdx) mouse hindlimb muscles. We aim to improve upon these results by using AOs to block splice sites flanking consecutive exons, in order to induce dystrophin which mimics that of revertant fibres. As most revertant transcripts are missing multiple exons, we believe that the functional capacity of AO-induced dystrophin can be improved upon by removing multiple exons. An mdx mouse skeletal muscle cell line is used for evaluation AOs. However, in order to determine the efficacy of the induced dystrophin in cardiac and skeletal muscle, experiments must be performed on mice. Previous work, in vitro and in muscles of mdx mice have validated this approach. Combinations of AOs which show promise will be delivered by a) intravascular injection b) intraperitoneal injection in mdx mice. The efficacy of the treatment will be assessed by both continual and end point analysis, which includes physiological, clinical, molecular and histological testing. Particular attention will be directed to the well-being of the mice and any adverse side effects which may occur.Read moreRead less
Probiotic Prophylaxis Of Spinal Cord Injury Urinary Tract-Infection TherapeUtic-Trial (ProSCIUTTU)
Funder
National Health and Medical Research Council
Funding Amount
$800,747.00
Summary
Urinary Tract Infections (UTI) are common in spinal cord injury (SCI) and about 2-year occur in SCI. Antibiotic resistance is also common in SCI. UTI are harder to treat with high rates of antibiotic resistance and this often leads to hospitalisation with significant health and economic consequences to the SCI community and country. Probiotics may prevent UTI and treat people colonised with resistant organisms. Unlike alternatives like antibiotics, they do not worsen antibiotic resistance.
Combined Electroacupuncture And Cognitive Behavioural Therapy For Tension-type Headache: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$302,068.00
Summary
Tension-type headache (TTH) affects many and the direct and indirect costs are significant. Medications are either not effective long-term or have side-effects. Acupuncture and Cognitive behavioural therapy (CBT) are effective and safe treatments. The combination of acupuncture and CBT could provide a better outcome. We will undertake a rigorous clinical study to evaluate this. This is the first examination of the combination, and will be of significant value to patients and to clinicians.
A Randomised Controlled Trial Of A Simplified Management Strategy Versus Standard Care In Moderate To Severe OSA
Funder
National Health and Medical Research Council
Funding Amount
$561,400.00
Summary
Currently breathing difficulties during sleep known as obstructive sleep apnea (OSA) are undertreated in our community. This reflects an inability of the current diagnostic and treatment strategies to deal with the high clinical burden of OSA. As a result, in particular in rural and remote areas, many have long waits for treatment, or no access to therapy at all. The purpose of this project is to evaluate a simplified protocol for the management of OSA. This will be done using diagnostic devices ....Currently breathing difficulties during sleep known as obstructive sleep apnea (OSA) are undertreated in our community. This reflects an inability of the current diagnostic and treatment strategies to deal with the high clinical burden of OSA. As a result, in particular in rural and remote areas, many have long waits for treatment, or no access to therapy at all. The purpose of this project is to evaluate a simplified protocol for the management of OSA. This will be done using diagnostic devices and treatment strategies that are more widely available than the current approaches to the diagnosis and management of obstructive sleep apnea. This will involve measurement of the numbers of falls in oxygen levels in a patient via a device to measure oxygen levels called an oximeter. These falls in oxygen levels correlate well with breath holding episodes during sleep characteristic of OSA. Treatment can be commenced in the patient's home depending on these results. We intend to compare these new approaches with the current best practice in OSA. If the outcomes are good these stategies could be applied to reduce the waiting times for to diagnose and manage OSA and make therapy more widely available throughout the community.Read moreRead less
Cancer arises through a combination of common DNA mutations which are associated with very poor survival in certain cancers. However, the cause of these mutations was always believed to be external factors (eg. UV light, toxins), Our exciting preliminary results show internal molecules, called circular RNAs, can drive these mutations and this project will investigate how this occurs and study whether targeting these molecules can reduce the incidence of cancers.
Circular RNAs As Genome Destabilisers In Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$2,163,220.00
Summary
Mutation of genes are hallmarks of both cancer and neurological disorders. My research group has identified roles for circular RNAs in both these processes. Now, we must close the loop by investigating the mechanism of these processes. This will inform not only why these genes are commonly mutated, but by exploiting the highly stable circular RNAs they may provide early prognostic/diagnostic biomarkers and even represent novel therapeutic targets for cancer and Huntington’s disease.
Targeting The Oncoprotein MDMX As A Novel Treatment For Triple Negative Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$561,672.00
Summary
Breast cancer (BrCa) is a leading cause of cancer death in women worldwide. BrCas unable to respond to current therapies have the worst outcomes. We propose a novel strategy to treat these cancers, based on our new findings. Our two protein targets are: (1) MDMX, that we found drives BrCa with its partner, (2) mutant p53, which causes cancer spread. We plan to directly target these drivers of aggressive BrCas, using new drugs that individually show great promise in trials in a number of cance