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Research Topic : blood-brain barrier
Scheme : NHMRC Development Grants
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  • Funded Activities (18)
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  • Funded Activity

    Improved Recovery And Storage Of Blood Bank Products

    Funder
    National Health and Medical Research Council
    Funding Amount
    $146,463.00
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    Funded Activity

    Use Of Snake Venom Prothrombin Activators In Blood Collection Tubes To Produce High Quality Serum To Improve Patient Outcomes

    Funder
    National Health and Medical Research Council
    Funding Amount
    $284,706.00
    Summary
    The timely availability of high quality serum and plasma samples are of the utmost importance for accurate biochemical analysis in a clinical setting. This requirement is particularly true for patients on anti-clotting therapeutic agents such as warfarin and heparin. In this study we will employ potent prothrombin activators purified from snake venom to enhance the clotting efficiency of blood for serum preparation for biochemical analysis.
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    Funded Activity

    Ultrasonic Blood Pressure Measurement On Implanted Biomedical Surfaces

    Funder
    National Health and Medical Research Council
    Funding Amount
    $170,250.00
    Summary
    The project would develop a prototype device reporting blood pressure on a biomedical implant surface. The device would extract data in real time from a standard ultrasound scanner that images the implant. The School of Mathematical Sciences at Monash University will be contracted to develop this ultrasound pressure sensor.
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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

    New Dynamometric Techniques For Predicting Glaucoma Progression

    Funder
    National Health and Medical Research Council
    Funding Amount
    $171,825.00
    Summary
    Glaucoma is a major cause of blindness in our community. The biggest risk factor for glaucoma is raised intraocular pressure. However, the exact cause of the disease remains unknown. Through our basic science studies in animals we have discovered that changes in blood flow in the vessels at the optic disk may be involved in the disease process. In recent clinical trials we discovered that the presence or absence of pulsations in the retinal veins at the disk was both an indicator of severity and .... Glaucoma is a major cause of blindness in our community. The biggest risk factor for glaucoma is raised intraocular pressure. However, the exact cause of the disease remains unknown. Through our basic science studies in animals we have discovered that changes in blood flow in the vessels at the optic disk may be involved in the disease process. In recent clinical trials we discovered that the presence or absence of pulsations in the retinal veins at the disk was both an indicator of severity and progression of glaucoma. This is a major breakthrough because there is no other means of predicting in which glaucoma patients vision loss will develop most rapidly. This information will be very helpful in deciding which patients should have the most agressive treatment to restore normal intraocular pressure. This project seeks to develop a new commercial device to make such an examination easy for any clinical ophthalmologist. The device allows the doctor to examine the vessels at the disk whilst applying slight pressure to the eye to temporarily raise intraocular pressure. A footswitch is pressed when the doctor sees the vessels pulsate. The required force is recorded by a laptop computer and the data stored along with the patients details. Now we have confirmed the ability of such a measurement to predict the rate of visual field loss in glaucoma, such a measurement will become much more widespread in clinical ophthalmology, offering a new and large scale opportunity for such instrumentation. Our device will be easy to operate, more comfortable for the patient, and will be of major diagnostic value in glaucoma clinics worldwide.
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    Funded Activity

    Test For Blood Poisoning

    Funder
    National Health and Medical Research Council
    Funding Amount
    $114,593.00
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    Funded Activity

    Development And Evaluation Of Novel Fetal Haemoglobin Inducers For The Therapy Of Beta-thalassaemia

    Funder
    National Health and Medical Research Council
    Funding Amount
    $288,899.00
    Summary
    The most important haemoglobinopathies from the clinical point of view are the beta-thalassaemias, sickle cell disease (SCD), HbE disease and the interactions between them. These beta-haemoglobinopathies are the result of mutations in the beta-globin gene, causing beta-globin chain synthesis that is abnormal, low or absent leading to life-threatening severe anaemia, and blood transfusion-dependency for life. An alternative approach to the therapy of beta-thalassemia is to reactivate fetal haemog .... The most important haemoglobinopathies from the clinical point of view are the beta-thalassaemias, sickle cell disease (SCD), HbE disease and the interactions between them. These beta-haemoglobinopathies are the result of mutations in the beta-globin gene, causing beta-globin chain synthesis that is abnormal, low or absent leading to life-threatening severe anaemia, and blood transfusion-dependency for life. An alternative approach to the therapy of beta-thalassemia is to reactivate fetal haemoglobin (HbF) synthesis. Some chemical agents have been identified to induce HbF and significantly reduce the need for blood transfusion in some thalassaemia patients, while in SCD patients it can ameliorate the clinical symptoms. Despite a number of clinical trials investigating the potential of HbF-inducing agents, many of these drugs have low efficacy, specificity, and cytotoxicity. There is therefore an urgent need to identify novel pharmacological agents with greater efficacy and reduced toxicity. Without a clear understanding of the underlying mechanism(s) involved in the induction of HbF, it is virtually impossible to focus on any molecular target. A promising approach is the use of chemical libraries in a high-throughput (HTP) screening to identify positive regulators of gene products. Our research group created an assay that has allowed us for the first time to perform a side-by-side comparison of several previously described fetal hemoglobin inducers including 2000 existing pharmaceuticals used by patients unrelated to thalassaemia. The screen identified a distinct group of compounds that induced the gamma-globin promoter in primary and secondary screens. The identification of novel inducers of HbF warrants further investigation as alternative therapies for beta-thalassemia. This project will evaluate novel inducers of HbF in our thalassaemia mouse model and provide early 'proof-of-concept' and enable the initiation of preclinical and clinical studies.
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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 A Fibre-optic Flow Sensor To Monitor Blood Platelet Adhesive Function.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $187,550.00
    Summary
    The ability to accurately diagnose platelet dysfunction is key to the clinical management of many cardiovascular diseases which represent a major cause of mortality in the industrialised world. At present there is no clinically robust instrument that can accurately assess abnormal platelet function under conditions that closely mimic the physiological environment. We aim to develop a sensitive prototype instrument for the clinical assessment of platelet function. We propose to develop this medic .... The ability to accurately diagnose platelet dysfunction is key to the clinical management of many cardiovascular diseases which represent a major cause of mortality in the industrialised world. At present there is no clinically robust instrument that can accurately assess abnormal platelet function under conditions that closely mimic the physiological environment. We aim to develop a sensitive prototype instrument for the clinical assessment of platelet function. We propose to develop this medical device as a relatively cheap and portable point of care instrument that can be marketed internationally.
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