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
Multiple sclerosis (MS) is the most common neurological disease of young adults, with very high costs in loss of quality of life, reduced contribution of sufferers to the workplace, and in treatment. No cures exist and its cause is unknown. It is, however, known to be a largely genetic disease - but the genes associated with it have yet to be identified. An international consortium, known as GAMES (Genes Associated with Multiple Sclerosis) has now completed a screen of all human chromosomes usin ....Multiple sclerosis (MS) is the most common neurological disease of young adults, with very high costs in loss of quality of life, reduced contribution of sufferers to the workplace, and in treatment. No cures exist and its cause is unknown. It is, however, known to be a largely genetic disease - but the genes associated with it have yet to be identified. An international consortium, known as GAMES (Genes Associated with Multiple Sclerosis) has now completed a screen of all human chromosomes using 6000 markers to identify regions with genetic differences in multiple sclerosis patients. The Australian contribution to this study was funded by the NHMRC. This project is a continuation of the first, only moving on to fine-scale mapping of the regions identified in GAMES1, so that single genes, rather than genetic regions, are the focus for the study. It also aims to ensure Australian participation as an equal player in phase II of this major international collaboration. The Australian results will contribute to the overall study. If associations identified in single countries are found in other countries, this confirms the validity of the association. In addition, genes which are only slightly associated with disease in individual countries, may become more meaningful if they are found to be associated in the studies from other countries. In this way a sensitive and robust comparison of the genes which affect predisposition to MS will be identified and this information can be used to target molecular pathways for drug intervention.Read moreRead less
Interrogation Of Two Novel Genetic Susceptibility Loci For Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$840,615.00
Summary
This proposal, from the Australia and New Zealand multiple sclerosis (MS) Genetics Consortium, aims to interrogate two new genes that it recently identified as predisposing for the development of MS. Both of the genes underlying these findings are also associated with risk of developing other autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and Graves' disease.
Identifying Genes In The HLA Complex That Influence Clinical Course And Susceptibility In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$725,177.00
Summary
There is no cure for multiple sclerosis (MS), but a person's genetic make-up can influence their susceptibility to developing MS and the symptoms of their condition. Knowing more about these MS genes will help to a) provide better advice concerning a person's risk of developing the disease or their prognosis b) in the design of new treatments. This project aims to identify 'MS genes in a region of the human genome call the HLA complex.
Localisation Of Genes For Multiple Sclerosis In The HLA Region
Funder
National Health and Medical Research Council
Funding Amount
$426,500.00
Summary
Multiple sclerosis (MS) is a disease that affects around 10,000 Australians. It is a disease of young adults with women being affected more often than men. While there are therapeutics available to treat it, these are very expensive ($10-12,000 per annum) and are effective in only a proportion of affected individuals. MS is governed by a complex interplay of environmental and genetic susceptibility factors, neither alone sufficient to cause disease, however, the study of these factors has been c ....Multiple sclerosis (MS) is a disease that affects around 10,000 Australians. It is a disease of young adults with women being affected more often than men. While there are therapeutics available to treat it, these are very expensive ($10-12,000 per annum) and are effective in only a proportion of affected individuals. MS is governed by a complex interplay of environmental and genetic susceptibility factors, neither alone sufficient to cause disease, however, the study of these factors has been confounded by the complex nature of the disease. We and other researchers have identified the human leukocyte antigen (HLA) complex on chromosome 6 as harbouring susceptibility genes for MS. Our recent work has localised these genes in two distinct regions of the HLA complex. In this project we plan to localise these genes more precisely to permit their identification. By identifying these genes we hope to develop an understanding of their function in a healthy person and in a person with MS. Understanding what goes wrong during disease is a critical first step along the track to the design of novel therapeutics. A successful therapeutic agent would be designed to interfere with disease processes and treat the disease more effectively.Read moreRead less
Studies On The Role Of The MIP-3beta/SLC System In The Priming Phase Of The Cytotoxic T Lymphocyte Response.
Funder
National Health and Medical Research Council
Funding Amount
$425,250.00
Summary
Generation of cytotoxic T cells (CTLs) is important for defence against viruses and cancer cells. However, when activated inappropriately, CTLs can contribute to diseases such as diabetes as well as transplant rejection. We intend to study the role of several recently-discovered proteins in this process. The outcome of this work may lead to the development of molecules that control CTL generation more specifically than existing therapeutics. Such inhibitors would potentially be useful in the tre ....Generation of cytotoxic T cells (CTLs) is important for defence against viruses and cancer cells. However, when activated inappropriately, CTLs can contribute to diseases such as diabetes as well as transplant rejection. We intend to study the role of several recently-discovered proteins in this process. The outcome of this work may lead to the development of molecules that control CTL generation more specifically than existing therapeutics. Such inhibitors would potentially be useful in the treatment of a range of human diseases.Read moreRead less