Understanding How Endogenous G-CSF Mediates Inflammatory Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$531,485.00
Summary
Rheumatoid Arthritis (RA) is a common chronic inflammatory disease which targets joints. Currently, there is no cure for RA and the available anti-rheumatic drugs have limited efficacy and frequent side effects. Progress has been made in understanding the molecular pathways which drive RA and the disease is characterised by high levels of inflammatory mediators (called cytokines). This finding has led to the development and introduction of specific cytokine inhibitors into clinical practice. The ....Rheumatoid Arthritis (RA) is a common chronic inflammatory disease which targets joints. Currently, there is no cure for RA and the available anti-rheumatic drugs have limited efficacy and frequent side effects. Progress has been made in understanding the molecular pathways which drive RA and the disease is characterised by high levels of inflammatory mediators (called cytokines). This finding has led to the development and introduction of specific cytokine inhibitors into clinical practice. These inhibitors work well for some, but not all, patients. The reason why certain RA patients fail to respond to this treatment is not clear. There is great interest in identifying new cytokines in RA and in developing more effective cytokine inhibitors. Our recent research shows that a cytokine best known for its effect on blood cell development (granulocyte-colony stimulating factor or G-CSF) also plays a major role in experimental models of RA. This discovery has led to two Australian biotechnology companies - Zenyth Therapeutics Ltd., and Murigen Therapeutics Ltd, entering into a partnership to develop G-CSF antagonists for clinical trials. However, before we can take such antagonists to the clinic, we need to conduct careful pre-clinical studies to understand the basis for our findings on G-CSF in much greater detail. This will ensure this new therapy is used in the safest and most effective way.Read moreRead less
Role Of The Hypoxia-inducible Transcription Factor HIF-1a In Controlling Haematopoietic Stem Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Haematopoietic stem cells (HSCs) reside in the bone marrow (BM) and make all immune and blood cells. We have found that, in the areas of the BM where HSC normally live, the level of oxygen is very low (hypoxia) and decreases even further when HSC are forced to move into the blood in order to be collected for transplantation. This project is to better understand how oxygenation of the BM controls HSC behaviour and properties, and to evaluate its impact on HSC transplantation.
Examining The Intracellular Pathways Regulated By GM-CSF In Macrophages And The Role In Diseases Such Arthritis.
Funder
National Health and Medical Research Council
Funding Amount
$63,567.00
Summary
A protein, termed GM-CSF, has been shown to be important in inflammatory conditions, like rheumatoid arthritis. GM-CSF can modify the properties of a key white blood cell, the macrophage, causing macrophages to produce factors harmful to host tissue. Various therapies are being developed to block GM-CSF, however discovering other drugs that block the intracellular actions of GM-CSF in macrophages are needed. Therefore the molecular pathways governing these actions need to be defined.