The proposed project is part of a research programme aimed at developing a new drug to reduce the side effects of cancer radiotherapy. These side effects result from the radiation damage to normal tissues close to the tumour. Since in many instances the normal tissues at risk are accessible to topical application (eg. skin in breast cancer patients, rectal mucosa in prostate cancer patients, oral mucosa in all patients being treated for tumours in the head and neck region) the concept is very si ....The proposed project is part of a research programme aimed at developing a new drug to reduce the side effects of cancer radiotherapy. These side effects result from the radiation damage to normal tissues close to the tumour. Since in many instances the normal tissues at risk are accessible to topical application (eg. skin in breast cancer patients, rectal mucosa in prostate cancer patients, oral mucosa in all patients being treated for tumours in the head and neck region) the concept is very simple. A drug which makes cells less sensitive to X-rays (these drugs are called radioprotectors) is simply applied topically to the normal tissues at risk. For this purpose, we have developed a new radioprotecting drug called methylproamine which is 100-fold more potent than previously-developed radioprotectors. Unfortunately, methylproamine is not suitable for our purpose because at higher concentrations it is toxic to some cells. This hurdle must be overcome in order to make the project attractive to potential commercial sponsors. Our aim is to modify methylproamine by removing the molecular features that cause the cytotoxicity. We have established that this is feasible, by synthesising and evaluating a small family of methylproamine analogues. Some less toxic family members have already been identified. With this knowledge, we now propose to use special computer programmes to design a much larger family of methylproamine analogues, and to synthesise and test each one in order to identify the most promising candidate for our purpose. Once the efficacy window hurdle is passed, the subsequent milestones to commercialisation and clinical implementation can be addressed, with appropriate sponsorship. An Australian company has already expressed strong interest and is evaluating the opportunity.Read moreRead less
Understanding Australia’s Drug Use: Prescription Psychotropics, Recreational Drugs And Novel Emerging Psychoactive Substances
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
Australians are consuming record levels of drugs that affect their mood and behaviour, both prescribed and illicit. They are also consuming an increasing array of novel synthetic drugs, the effects of which are largely unknown. Professor Iain McGregor engages in innovative research that examines the drugs we take, their effects on the brain, and their risks and benefits. His team also develops new medications that may become future treatments for anxiety, depression and addictions.
Mapping And Manipulating Circuits For Relapse And Abstinence
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
Alcohol-use disorders and other drug addictions are chronically relapsing conditions. Current treatment approaches have only modest efficacy. Two advances are needed for genuine improvement. The first is parsing the brain mechanisms supporting abstinence and relapse at cellular as well as circuit levels. The second is targeting these circuits therapeutically with the same precision. This project contributes to the first advance and lays a basic science platform for next generation therapeutics.
Overcoming Radiation Resistance In Glioblastoma With Novel Metabolic Modulations
Funder
National Health and Medical Research Council
Funding Amount
$62,554.00
Summary
Aim 1 is to document the pathological, surgical, radiotherapy and chemotherapy patterns of care in the Australian setting using the AGOG (Australian Genomics and Clinical Outcomes of Glioma) database. The second aim to develop non-invasive imaging biomarkers which can be used to monitor treatment efficacy. The third aim is to improve outcomes using drug and radiation combination therapy. in the treatment of high grade gliomas.
Huntington’s disease is a devastating neurological disorder, with no drugs currently available to cure or treat the underlying cause. Our recent laboratory work on a drug called PBT2 was the foundation of a encouraging clinical trail for this disease. Here, we propose to investigate a drug called Zn(DTSM) for this disease, which has similar properties to PBT2, but we expect will have a greater effect.
Investigating The Cause And Consequences Of Iron Deposition In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$459,347.00
Summary
It is known that iron elevation occurs in the brain in Parkinson’s disease. This might cause cell death by ‘rusting’. It is not known (1) how iron accumulates in the disease, (2) whether iron accumulation contributes to the worsening of the disease and (3) if lowering iron with a drug would improve symptoms. We plan to address these questions using a clinical cohort of patients, and laboratory animal models.
Novel System For Non-Invasive Delivery Of Drugs To The Interior Of The Eye
Funder
National Health and Medical Research Council
Funding Amount
$200,213.00
Summary
Age-related macular degeneration (AMD) is the leading cause of visual loss for adults in the developed world. Treatment is now by needle injection into the back of the eye, which is painful for the patient and is costly for the health-care system. Seagull Technology Pty Ltd has developed a non-invasive device for treating the back of the eye without the need for a needle injection. This project will test the new device in animals and then move to a first safety study for human AMD patients.
Assessment Of Development Of Resistance To Neuraminidase Inhibitors In A (H5N1) Influenza Viruses Using A Ferret Model
Funder
National Health and Medical Research Council
Funding Amount
$165,546.00
Summary
The neuraminidase (NA) inhibitors are considered the most effective anti-influenza drugs available for both prevention and treatment of influenza virus infection including A(H5N1) viruses. The drugs are effective against all subtypes of influenza A, making them ideal for use in the early months of a pandemic prior to an appropriate vaccine being produced. As a result many countries around the world, including Australia, have stockpiled these drugs (mainly Tamiflu) as part of their pandemic prepa ....The neuraminidase (NA) inhibitors are considered the most effective anti-influenza drugs available for both prevention and treatment of influenza virus infection including A(H5N1) viruses. The drugs are effective against all subtypes of influenza A, making them ideal for use in the early months of a pandemic prior to an appropriate vaccine being produced. As a result many countries around the world, including Australia, have stockpiled these drugs (mainly Tamiflu) as part of their pandemic preparedness plans. However, of concern is the increasing number of recent reports of a higher than expected level of resistance in epidemic influenza being generated against these drugs. A recent isolation of an H5N1 virus from a Vietnamese girl highlights that these viruses can also be resistant to Tamiflu. Within Australia, Tamiflu will be a critical weapon against the initial wave of an influenza pandemic, therefore it is vital that more is known about the propensity of the H5N1 virus to generate resistance, and possibly make these drugs clinically less effective. The aim of the project is to determine the levels, mode and type of resistance that may occur when ferrets are experimentally infected with HP A(H5N1) virus and then treated with NA inhibitors drugs such as Tamiflu. In the event of resistant viruses being isolated following drug pressure from Tamiflu, the strains will then be tested for their sensitivity to the other NA inhibitor drugs Relenza (zanamivir) or the peramivir (a third currently unlicensed NA inhibitor). The results from this cross resistance work will allow strategies to be put into place regarding the administration of an alternative NA inhibitor in the event of a pandemic virus acquiring particular NA mutations which may for example result in Tamiflu resistance. To determine the relative human risk of a NA inhibitor resistant A(H5N1) virus, studies to determine how infectious or transmissible the viruses are would be performed on all resistant strains isolated. NA inhibitor resistant strains demonstrate varying degrees of transmissibility and fitness, therefore it would be beneficial to classify this for any strains generated from this study so as to be in a better position to understand the public health implications if a particular resistant strain was to arise.Read moreRead less