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Research Topic : brain disorders
Scheme : NHMRC Development Grants
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  • Funded Activity

    A Motion Correction Technique For Accurate PET/CT Brain Imaging In Paediatric And Dementia Patients

    Funder
    National Health and Medical Research Council
    Funding Amount
    $190,450.00
    Summary
    PET-CT imaging is a vital tool in the diagnosis and management of patients with brain disorders including dementia, epilepsy and cancer. However images are often distorted by patient motion, particularly in demented and paediatric patients. The CI has recently developed a motion tracking and correction method to derive images nearly free of motion effects. This aim of this project is to evaluate its impact on image quality in a variety of patients referred for PET- CT brain investigations.
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    Funded Activity

    A Device For Simultaneous Continuous Acquisition Of EEG And MRI

    Funder
    National Health and Medical Research Council
    Funding Amount
    $179,401.00
    Summary
    We aim to further develop a world-leading method we invented that facilitates the simultaneous, continuous acquisition of the electroencephalogram (EEG - electrical brain waves measured at the scalp) and functional Magnetic Resonance Imaging (fMRI - images the location of brain activity throughout the brain). Combining the two permits non-invasive imaging of human brain function with the exquisite temporal resolution of EEG and the high spatial resolution and brain coverage afforded by fMRI.
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    Funded Activity

    Commercial Testing Of A Physiologically Based Theory Of Oscillatory Brain Electrical Activity In Anaesthesia Monitoring

    Funder
    National Health and Medical Research Council
    Funding Amount
    $191,165.00
    Summary
    While the mechanisms of local anaesthesia are comparatively well known, the mechanisms whereby anaesthetics impair consciousness remain unresolved. This lack of understanding has implications in our ability to monitor the level of anaesthesia while anaesthetic consumption and side effects are minimized. Despite this a number of devices have been developed that attempt to monitor the depth of anaesthesia by quantifying the brains electrical activity. All monitors analyse the activity using a set .... While the mechanisms of local anaesthesia are comparatively well known, the mechanisms whereby anaesthetics impair consciousness remain unresolved. This lack of understanding has implications in our ability to monitor the level of anaesthesia while anaesthetic consumption and side effects are minimized. Despite this a number of devices have been developed that attempt to monitor the depth of anaesthesia by quantifying the brains electrical activity. All monitors analyse the activity using a set of criteria that have been developed by trial and error. The research of Dr David Liley and his team, at Swinburne University of Technology, has resulted in a detailed understanding of the physiological mechanisms that generate brain electrical activity. The outcome is a practical means to carry out a System Based Analysis of Brain Electrical Response (SABER). In 2004, Dr Liley began working with Cortical Dynamics, a company involved in the commercialisation of medical devices. This collaboration incorporated the SABER system into a new prototype device called the Brain Anaesthesia Response (BAR) monitor. In 2004 Dr Liley and Associate Professor Kate Leslie collaborated in a trial, at the Royal Melbourne Hospital to test the sensitivity of the SABER system in quantifying the effect that various levels of nitrous oxide have on measures of anaesthetic depth. The Australian and New Zealand College of Anaesthetists supported this study. Initial results obtained with sevoflurane and 3 levels of nitrous oxide showed the ability to differentiate between conscious and unconscious states of patients based on two physiological characterizations of higher brain dynamic state. The next step requires commercial product validation (ie scale up) and further clinical efficacy in testing beta stage depth of anaesthesia BAR units. Completion of this will help the technology move away from a low volume prototype system into a commercially applicable device.
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    Funded Activity

    Se015: A Developmental Drug For The Treatment Of Brain Tumours

    Funder
    National Health and Medical Research Council
    Funding Amount
    $304,206.00
    Summary
    Primary malignant brain tumors are amongst the most lethal forms of human cancers with median survival for these patients being only around 1 year. In spite of the advent of new targeted therapies for some cancers the prognosis for these patients remains dismal. Worldwide, more than 95% of all people who contract the disease will die of it. This is because there are no effective therapies and all current treatments are only palliative, seeking to lesson the distressing suffering associated with .... Primary malignant brain tumors are amongst the most lethal forms of human cancers with median survival for these patients being only around 1 year. In spite of the advent of new targeted therapies for some cancers the prognosis for these patients remains dismal. Worldwide, more than 95% of all people who contract the disease will die of it. This is because there are no effective therapies and all current treatments are only palliative, seeking to lesson the distressing suffering associated with disease progression. Nearly all therapies that have shown some efficacy in treating cancer, such as chemotherapy and radiation have a mode of action whereby they attempt to kill cancer cells by inflicting enough damage to the cancer cells that they induce them to commit cell suicide, a process called apoptosis. Unfortunately, cancer cells can become resistant to these therapies by activating the cells' own signaling pathways that normally block apoptosis. One of the key pathways that has been implicated in resistance to apoptosis in human cancers is the PI3K-Akt pathway. This pathway is overactivated in many advanced human tumors, particularly in glioblastoma. We have discovered a compound, Se015, which can effecitively block this pathway in brain cancer cells and is able to dramatically improve the effectiveness of both chemotherapy and radiation in killing these cells. We have confirmed the efectiveness of Se015 in preliminary animal models of brain cancer, where we have shown that Se015 demonstrated no noticeable toxicity and was active when taken orally. We now need to explore further the molecular mode of action of Se015, as well as complete our animal studies with the eventual aim of initiating a small trial of Se015 in glioblastoma patients in the forseeable future.
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    Funded Activity

    Automated Seizure Detection In The Newborn.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $243,750.00
    Summary
    Newborn babies are at risk of becoming short of oxygen during delivery and sustaining brain damage. Seizures may cause further damage to the brain because they release damaging chemicals or make extra energy demands on the brain that cannot be met. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain. We are proposing to automatically detect and count seizures, building upon 8 years of fundamental EEG signal processing research work we have undertake .... Newborn babies are at risk of becoming short of oxygen during delivery and sustaining brain damage. Seizures may cause further damage to the brain because they release damaging chemicals or make extra energy demands on the brain that cannot be met. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain. We are proposing to automatically detect and count seizures, building upon 8 years of fundamental EEG signal processing research work we have undertaken. We anticipate that the product will be of major commercial interest. We will further explore what is a rapidly expanding marketplace and ensure we maximize the commercial return on this product.
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    Funded Activity

    Development Of Small Molecule IRAP Inhibitors For Treating Memory Deficits

    Funder
    National Health and Medical Research Council
    Funding Amount
    $369,898.00
    Summary
    We have identified a series of small molecule compounds based on their ability to inhibit the catalytic activity of a protein, IRAP using a computer model of IRAP to screen chemical libraries. This research proposal aims to investigate the properties of these compounds and their ability to treat Alzheimer's dementia. At the conclusion of this project, we will have 2 families of lead compounds suitable for development into a new class of therapeutic agents for treating Alzheimer's disease.
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    Funded Activity

    Development Of Small Molecule Inhibitors Of IRAP - Potential Use For The Treatment Of Memory Disorders

    Funder
    National Health and Medical Research Council
    Funding Amount
    $195,450.00
    Summary
    This research project provides proof of concept that IRAP is a suitable target for use in the development of a new class of clinically valuable cognitive-enhancing agents. We have recently Identified a family of small molecule compounds that inhibited the catalytic activity of the enzyme using a molecule model of IRAP to screen virtual libraries. This research proposal aims to validate that this family of compounds have memory-enhancing properties by acting specifically on IRAP. At the conclusio .... This research project provides proof of concept that IRAP is a suitable target for use in the development of a new class of clinically valuable cognitive-enhancing agents. We have recently Identified a family of small molecule compounds that inhibited the catalytic activity of the enzyme using a molecule model of IRAP to screen virtual libraries. This research proposal aims to validate that this family of compounds have memory-enhancing properties by acting specifically on IRAP. At the conclusion of this project, we will have elucidated important information on the specificity of the memory effects and the structure activity relationship of this family of compounds. We will have identified and characterised a lead compound for development into a new class of cognitive enhancers.
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    Funded Activity

    Novel Methods For Promoting Organ Development And Growth

    Funder
    National Health and Medical Research Council
    Funding Amount
    $390,203.00
    Summary
    A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of Colony Stimulating Factor (CSF-1). We have evidence that CSF-1 therapy can promote kidneys and lungs to continue development and maturation after birth. This exciting new finding allows for the application of CSF-1 therapy for both the treatment of premature babies and unborn babies with kidney defects.
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    Funded Activity

    Development Of A Novel Diagnostic Test For The Death Of Neuromelanin-containing Dopamine Neurons In The Human Brain

    Funder
    National Health and Medical Research Council
    Funding Amount
    $325,308.00
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    Funded Activity

    Rapid, Cost-effective, Diagnosis And Monitoring Of Multiple Sclerosis By Novel Multifocal Evoked Potential Methods

    Funder
    National Health and Medical Research Council
    Funding Amount
    $152,463.00
    Summary
    A new technology for concurrently stimulating both eyes, and recording thousands of responses from the brain, will be tested for its effectiveness in diagnosing and tracking progression in Multiple Sclerosis (MS), and the degree to which it complements Magnetic Resonance Imaging (MRI). Our understanding of MS has changed in recent years. It is now recognised to have two phases: an initial inflammatory phase, and a secondary progressive phase. The progressive phase produces the inexorable increas .... A new technology for concurrently stimulating both eyes, and recording thousands of responses from the brain, will be tested for its effectiveness in diagnosing and tracking progression in Multiple Sclerosis (MS), and the degree to which it complements Magnetic Resonance Imaging (MRI). Our understanding of MS has changed in recent years. It is now recognised to have two phases: an initial inflammatory phase, and a secondary progressive phase. The progressive phase produces the inexorable increasing disability of MS. MS only affects about 0.04% of Australians but the early onset of MS, the high cost of medication, and the prolonged period of disability, mean that the cost to Australia is about $2 billion pa. MRI quantifies the inflammatory phase well but is poorly correlated with the debilitating secondary progression. The common treatments for MS target the inflammatory phase but not the causes of secondary progression, which are unknown. Current diagnostic methods mean diagnosis can take years, meaning that patients can be denied treatment for some time. The applicants have published experiments on 50 MS patients and 27 normal subjects using a variant of the new method. Not only has it shown high diagnostic accuracy, but the new method seems to provide data on the progressive phase, suggesting strongly that it is complementary to MRI. The new method is also much cheaper to set up and run than MRI and so could provide cost-effective means for monitoring patient condition and testing new drugs that are effective against the progressive phase. The applicants have considerable experience commercialising diagnostic technologies, and are currently working with an Australian company developing new diagnostic hardware. That hardware has been adapted to perform the presently proposed experiments. Overall it is reasonable to assume that positive outcomes will be translated into economic and health benefits for Australians.
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