Immune-modifying-particle-induced Tregs Induce Remission In Experimental Autoimmune Encephalomyelitis
Funder
National Health and Medical Research Council
Funding Amount
$512,440.00
Summary
Multiple Sclerosis is a debilitating autoimmune disease of the central nervous system. Disease is the result of inflammatory monocyte-derived dendritic cells that migrate from the blood into the brain, where they stimulate T cells to attack myelin sheaths around neurons. Our novel therapy, known as immune modulating micro-particles reduces monocyte migration and disease in a mouse model, we hypothesize, by inducing immunosuppressive T regulatory cells that control attacking T cells in MS.
Immune Tolerance In Experimental Autoimmune Encephalomyelitis Following Transplant Of Bone Marrow Cells Genetically Encoding Autoantigen
Funder
National Health and Medical Research Council
Funding Amount
$339,143.00
Summary
Autoimmune diseases affect 5-6% of the population and include diseases such as multiple sclerosis. Our studies focus on examining a gene therapy approach together with bone marrow transplantation to treating autoimmune diseases. Using a model for multiple sclerosis we are finding promising results
Multiple Sclerosis Therapy: Human Pluripotent Stem Cell-Derived Neural Precursor Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,775,225.00
Summary
Treatments for Multiple Sclerosis (MS) often have unsatisfactory outcomes. The limited ability of the body to repair damaged nerve tissue highlights a critically important need for MS patients. The long-term goal of our research is to develop a stem cell-based therapy that halts disease progression and repairs damaged nerve tissue. Research efforts will refine techniques to make safe and clinically-compatible cells from human stem cell lines and verify the therapeutic activity of these cells.
Regulation Of The Anti-tumour Immune Response By The Chemokine Decoy Receptor CCX-CKR
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Melanoma is a significant cause of cancer-related deaths in Australians. Death is usually due to metastasis of the cancer to the lungs and other organs. In this project, we will take advantage of unique mouse models to determine whether inhibition of the function of a novel protein can prevent melanoma growth and metastasis to different organs. The results of this study may lead to new therapeutic approaches to control malignant melanoma and other metastatic cancers.
In autoimmune diseases the immune system attacks the body’s own tissues. Although we know that both genetic and environmental factors contribute to the risk of disease, identifying these genes and the environmental factors involved is very difficult. Furthermore, we have almost no idea how these factors interact with each other, something we need to understand in order to predict the risk of disease and reliably identify possible therapies. These are the aims of this fellowship.
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
Regulation Of Astrocytic Gliosis And Axonal Regeneration In EAE By EphA4
Funder
National Health and Medical Research Council
Funding Amount
$532,352.00
Summary
Multiple Sclerosis (MS) is a debilitating disease with currently no effective cure. Apart from losing the protective insulating sheath called myelin, nerve cells are damaged and a scar forms. If this could be prevented then MS may be better treated. Using a model of MS called EAE, the role of a molecule, EphA4, will be examined for its ability to induce nerve loss and scar formation and to determine whether blocking it will promote repair, leading to a therapy for MS.
Current therapy for AAV has major toxicities and 30% of Patients are dead or on dialysis within 3 years. This proposal aims to study a unique form of cell death termed Neutrophil extracellular traps (NETs) that initiates and perpetuates inflammation in this disease. We will use an animal model of the disease that mirrors human disease. We will inhibit crucial molecules in NET production to attenuate disease. This will provide proof of concept evidence to promote clinical trials in patients.
Control and effective treatment of autoimmune diseases remain major challenges to our health system. Diseases such as multiple sclerosis, systemic lupus erythematosus, diabetes and pernicious anaemia are serious conditions that are essentially incurable. Current treatment is only effective in providing temporary relief as it is not directed against the underlying disease process. This project will manipulate the immune system in such a way that early disease processes in autoimmunity will be blo ....Control and effective treatment of autoimmune diseases remain major challenges to our health system. Diseases such as multiple sclerosis, systemic lupus erythematosus, diabetes and pernicious anaemia are serious conditions that are essentially incurable. Current treatment is only effective in providing temporary relief as it is not directed against the underlying disease process. This project will manipulate the immune system in such a way that early disease processes in autoimmunity will be blocked with the ultimate goal to cure the disease. Using an experimental model of pernicious anaemia in mice, where the basic pathology is immune-mediated gastritis, the disease will be treated by presenting the disease causing autoantigen via modified, or immature, antigen presenting cells to the immune system. In other experimental models which form the background to this project we have shown that this approach leads to down-regulation of the immune response by generating cells which specifically suppress the immune system. In our studies of autoimmune gastritis we will obtain modified antigen presenting cells from the skin, the blood, the spleen and thymus and use these cells to define optimal conditions for presenting the auto-antigen molecules to achieve the ultimate goal, which is antigen specific suppression of autoimmune gastritis. Our hypothesis is that immature antigen presenting cells are unable to present antigen to induce an effective immune response, but instead induce a response that results in antigen specific suppression. We intend to use this antigen specific suppression to prevent the establishment of autoimmune gastritis as well as treatment of established disease. This is a unique and potentially valuable strategy to treat autoimmune gastritis and offers the potential to apply this approach to other autoimmune conditionsRead moreRead less
Targeting Tregs Using Chimeric Antigen Receptors (CARs) For The Treatment Of Autoimmune Renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$845,519.00
Summary
Chronic Kidney Disease is one of the major causes of death in Australia. Therapeutic success with regulatory T cells (Tregs) capable of targeting autoimmune kidney disease would have major clinical implications. In the proposed study, we will use Chimeric Antigen Receptors (CARs) T cells by redirecting them to diseased organs, protect against kidney injury. These CAR T cells will recognise renal antigens and target immune cells and antibodies to limit kidney damage.