An integrated platform built on efficient informatics concepts already implemented in international research infrastructures for large-scale data management, providing access to federated databases/registries, biobank catalogues, harmonised - omics profiles, and bioinformatics tools. Patient data types will be linked via a unique identifier “RD-ID” developed jointly with the US NIH. RD-Connect is a primary enabler for IRDiRC funded research to improve treatment and management of rare diseases
The Role Of Interferon Gamma And Nitric Oxide As Downregulating Molecules In Central Nervous System Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$526,644.00
Summary
Cytokines are soluble factors which participate in inflammatory responses. Interferon gamma is a cytokine which in the context of central nervous system inflammation has been considered a Obad? molecule, as has the gas nitric oxide which is induced by interferon gamma. We now have direct evidence that indicate quite the contrary, ie interferon gamma and nitric oxide can a do act as down regulators of inflammation. The present work is designed to determine if this down regulating function is rest ....Cytokines are soluble factors which participate in inflammatory responses. Interferon gamma is a cytokine which in the context of central nervous system inflammation has been considered a Obad? molecule, as has the gas nitric oxide which is induced by interferon gamma. We now have direct evidence that indicate quite the contrary, ie interferon gamma and nitric oxide can a do act as down regulators of inflammation. The present work is designed to determine if this down regulating function is restricted only to a single model of CNS inflammation or is a general phenomenon within the CNS. The project will also involve a number of experiments designed to elucidate the mechanism(s) by which down regulation occurs. This project is highly significant in that a single uncontrolled clinical trial of interferon gamma for the therapy of MS has been carried out and reported as indicating that interferon gamma made the disease worse. The design of that trial however was such that the validity of that claim is questionable. If our experiments confirm the general nature of interferon gamma as a down regulator in inflammation in a number of different models of MS then a case for revisiting the use of interferon, or a downstream product of interferon, in the therapy of MS might be made.Read moreRead less
Pharmacological Strategies To Prevent Damage To White Matter In The Central Nervous System After Ischaemia
Funder
National Health and Medical Research Council
Funding Amount
$150,770.00
Summary
A stroke is caused by an acute blockade of blood flow to a brain region and in most cases, is caused by a clot in the artery that supplies the oxygenated blood and nutrients such as glucose to that region. Within minutes, the region of the brain that is deprived of blood flow will die and so the functions controlled by that region are lost. In the majority of stroke patients, the middle cerebral artery is blocked and this affects parts of the brain controlling movement of limbs or speech and so ....A stroke is caused by an acute blockade of blood flow to a brain region and in most cases, is caused by a clot in the artery that supplies the oxygenated blood and nutrients such as glucose to that region. Within minutes, the region of the brain that is deprived of blood flow will die and so the functions controlled by that region are lost. In the majority of stroke patients, the middle cerebral artery is blocked and this affects parts of the brain controlling movement of limbs or speech and so these patients suffer permanent disabilities. Not surprisingly, stroke is the most common life-threatening neurological disease and the major cause of disbility in adults over 45 years of age. Apart from the profound effect that stroke has on the patient and family, the annual cost of disability to the Australian community is approximately $ 1 billion. If the disability could be reduced, this could reduce the need for institutionalisation of patients and then the cost saving would be great. So our research is directed towards designing drugs to minimise the disability after stroke. Research in the past has focussed on designing drugs to minimise damage to the grey matter in brain but it is becoming apparent that the white matter in brain is very important for transmitting information and also needs to be protected. We will study the biochemical changes in white matter after a stroke in a rat model and use this information to design in a rational way, novel drugs to minimise damage to white matter (axons), thereby reducing the degree of disability after a stroke.Read moreRead less
Defining The Basis Of Autoimmune Attacks Against Myelin To Better Target Treatment Of Demyelinating Disorders
Funder
National Health and Medical Research Council
Funding Amount
$913,216.00
Summary
Brain autoimmunity is a common and costly cause of neurological and psychiatric disability in children and adults. Exploring the autoimmune response that targets the brain is essential for accurate diagnosis, prognosis, and treatment. This project grant will identify and study the earliest autoimmune responses against the brain in children and adults. This will allow early and directed treatments that will not only prevent disability, but will also be life-saving.
Modulation Of BMP Signaling For Enhanced Myelin Repair
Funder
National Health and Medical Research Council
Funding Amount
$656,623.00
Summary
Multiple Sclerosis is the most common neurodegenerative disease affecting young adults. It is a disease that kills myelin cells, which are necessary support cells for neurons and are critical for their function. This research investigates the role that the signal transduction of bone morphogenic protein plays in myelin cell production and myelin repair. Our aim is to identify regenerative therapeutics for Multiple Sclerosis.
Developing A New Strategy For Treating Demyelinating Peripheral Diseases
Funder
National Health and Medical Research Council
Funding Amount
$496,250.00
Summary
Incomplete remyelination is a significant component of the persistent clinical disability of peripheral demyelinating neuropathy, contributing to conduction deficits and the secondary axonal damage. A crucial therapeutic challenge is to identify ways to promote remyelination. This project aims to develop a new strategy and a novel clinically relevant target for treating peripheral demyelinating neuropathy.
The Role Of BDNF In Central Nervous System Myelination
Funder
National Health and Medical Research Council
Funding Amount
$478,235.00
Summary
Multiple Sclerosis (MS) is the most common neurological cause of disability in young adult Australians. The cause of MS is unknown and therapies are limited to reducing inflammation, which does not address the major problem of the disease: loss of myelin. This project directly investigates how myelin is formed and will identify key mechanisms in this process, which may eventually be developed into treatments for diseases such as MS.
T Cell Apoptosis In Multiple Sclerosis And Experimental Autoimmune Encephalomyelitis
Funder
National Health and Medical Research Council
Funding Amount
$299,950.00
Summary
Multiple sclerosis is a disease of the nervous system and is a common cause of disability in young adults. There is increasing evidence that multiple sclerosis is caused by repeated attacks on the nervous system by the white blood cells (lymphocytes) of the body's own immune system. A major unanswered question in multiple sclerosis is why repeated immune attacks on the nervous system occur. I have recently proposed that the repeated nature of the immune attacks in multiple sclerosis results from ....Multiple sclerosis is a disease of the nervous system and is a common cause of disability in young adults. There is increasing evidence that multiple sclerosis is caused by repeated attacks on the nervous system by the white blood cells (lymphocytes) of the body's own immune system. A major unanswered question in multiple sclerosis is why repeated immune attacks on the nervous system occur. I have recently proposed that the repeated nature of the immune attacks in multiple sclerosis results from a failure of the mechanism that switches off immune attacks on the nervous system in healthy individuals. In an animal model of multiple sclerosis we have shown that the lymphocytes attacking the nervous system rapidly commit suicide in the nervous system by a process known as apoptosis, and that this is associated with switching off of the immune attack and recovery from the disease. The present project aims to study further this process of lymphocyte suicide in experimental animals by determining whether the lymphocyte suicide is mediated through a death receptor molecule named Fas (CD95). The project will also investigate the process of lymphocyte suicide in white blood cells obtained from patients with multiple sclerosis to determine if this process is defective and to determine whether these patients have abnormalities in the Fas molecular pathway. This project will shed light on the question of why repeated immune attacks on the nervous system occur in multiple sclerosis, and has the potential to lead to the development of new treatments for multiple sclerosis.Read moreRead less
Investigation Of The Functional Role Of Antibodies Against Myelin Proteolipid Protein In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$626,174.00
Summary
There is a lot of suggestive evidence that molecules called antibodies might cause a faster progression of disease in people with multiple sclerosis (MS), but this remains to be proven. The proposed study will investigate the mechanisms by which antibodies could hasten MS disease progression. Results of this study will help inform treatment options for people with MS and will also help us to better understand the basic pathogenic mechanisms that can cause MS.
Pathogenesis Of Inflammatory Demyelinating Polyneuropathy
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
This project will investigate the cause of Guillain Barre syndrome (GBS), a severe disease that causes paralysis of the limbs, and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), a similar disease that causes either repeated attacks of weakness or chronic weakness. These are important diseases of the peripheral nervous system. In GBS and CIDP, white blood cells move from the bloodstream to phagacytose (eat) the myelin that surrounds peripheral nerve fibres. Removal of myelin interferes ....This project will investigate the cause of Guillain Barre syndrome (GBS), a severe disease that causes paralysis of the limbs, and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), a similar disease that causes either repeated attacks of weakness or chronic weakness. These are important diseases of the peripheral nervous system. In GBS and CIDP, white blood cells move from the bloodstream to phagacytose (eat) the myelin that surrounds peripheral nerve fibres. Removal of myelin interferes with normal function of the nerves. The project will investigate 5 aspects of GBS and CIDP. (1) We will determine which component of myelin is recognised by white blood cells from patients with GBS and CIDP. We have performed preliminary studies indicating that a protein known as PMP-22 and gangliosides may be targets of the immune attack, but this needs to be confirmed. (2) We will study how the immune attack is turned off in GBS. (3) We will study whether and why the immune attack fails to be turned off in CIDP. (4) We will identify genetic markers that may predispose to GBS and CIDP. (5) We will investigate a novel animal model of GBS that we have induced in rats by inoculation with fragments of PMP-22 protein.Read moreRead less