Development Fo A Novel Treatment For Asthma: The Identification Of Lead Small Molecule Antagonists Of The IL-13/IL-13 Re
Funder
National Health and Medical Research Council
Funding Amount
$99,750.00
Summary
In developed countries Asthma ranks among the most common chronic illnesses. Over two million Australians now have this condition and the cost to our community is estimated to be in excess of $720 million per annum. In 1996 researchers at The Walter and Eliza Hall Institute discovered a new member of the cytokine receptor family, IL-13Ra1, which further research has strongly implicated in the pathology of this disease. The main goal of the proposed research is to discover small molecule antagoni ....In developed countries Asthma ranks among the most common chronic illnesses. Over two million Australians now have this condition and the cost to our community is estimated to be in excess of $720 million per annum. In 1996 researchers at The Walter and Eliza Hall Institute discovered a new member of the cytokine receptor family, IL-13Ra1, which further research has strongly implicated in the pathology of this disease. The main goal of the proposed research is to discover small molecule antagonists of IL-13Ra1 and to identify those suitable for development as novel asthma therapeutics.Read moreRead less
Development And Biological Evaluation Of Cytokine Macrophage-migration Inhibitor (MIF) Non-Steroidal Antagonists
Funder
National Health and Medical Research Council
Funding Amount
$85,000.00
Summary
The cytokine macrophage-migration inhibitory factor (MIF) has a broad range of pro-inflammatory effects in the innate and adaptive immune system. CIA’s lab has demonstrated the potential importance of MIF in the pathology of chronic inflammation via studies in models of rheumatoid arthritis (RA). Similarly to other chronic inflammatory diseases, MIF is overexpressed in human RA, and induces activation of key pathological processes in RA cells. Moreover, antagonism of MIF with mAb profoundly inhi ....The cytokine macrophage-migration inhibitory factor (MIF) has a broad range of pro-inflammatory effects in the innate and adaptive immune system. CIA’s lab has demonstrated the potential importance of MIF in the pathology of chronic inflammation via studies in models of rheumatoid arthritis (RA). Similarly to other chronic inflammatory diseases, MIF is overexpressed in human RA, and induces activation of key pathological processes in RA cells. Moreover, antagonism of MIF with mAb profoundly inhibits models of RA and other inflammatory diseases, confirming MIF as a therapeutic target in human inflammatory disease. The X-ray crystal structure of MIF has been published and the putative active site fully characterised. We have deduced structural features of MIF that reveal aspects of the structural complementarity of host-guest affinity. This information has been used in the synthesis of new compounds to antagonise MIF. We have designed, synthesised and tested several classes of compounds, which have shown activity from milli to nano-molar levels in novel in-house in vitro bioassays.Read moreRead less
Seminal Plasma Cytokines As Novel Fertility Diagnostics In Men
Funder
National Health and Medical Research Council
Funding Amount
$101,000.00
Summary
Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Current IVF therapy is not successful when the underlying reason for infertility is failure of the maternal tissues to support embryo implantation. We have discovered signaling proteins present in male semen that act in the female reproductive tissues to prepare for embryo implantation and healthy pregnancy. Recently we have identified those proteins and have shown that some men ha ....Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Current IVF therapy is not successful when the underlying reason for infertility is failure of the maternal tissues to support embryo implantation. We have discovered signaling proteins present in male semen that act in the female reproductive tissues to prepare for embryo implantation and healthy pregnancy. Recently we have identified those proteins and have shown that some men have an imbalance in seminal proteins that leads to immune rejection of the embryo in the female partner. This project aims to develop a new test for male fertility that is based on seminal plasma proteins and independent of existing sperm count tests. Furthermore we will determine whether seminal protein imbalance can result from the �silent� presence of male reproductive tract infection.Read moreRead less
Development And Pre-clinical Evaluation Of G-DSF Inhibitors For Inflammatory Joint Disease
Funder
National Health and Medical Research Council
Funding Amount
$88,329.00
Summary
G-CSF was originally identified as a cytokine regulating the production of neutrophils and haemopoietic stem cells from the bone marrow and it is currently used clinically for these properties in bone marrow transplant patients around the world. Anti-cytokine therapy with TNF blockade has recently been introduced for the treatment of rheumatoid arthritis. However, not all patients respond to TNF inhibition. We have gathered extensive data which shows that G-CSF also promotes inflammation in expe ....G-CSF was originally identified as a cytokine regulating the production of neutrophils and haemopoietic stem cells from the bone marrow and it is currently used clinically for these properties in bone marrow transplant patients around the world. Anti-cytokine therapy with TNF blockade has recently been introduced for the treatment of rheumatoid arthritis. However, not all patients respond to TNF inhibition. We have gathered extensive data which shows that G-CSF also promotes inflammation in experimental models of inflammatory joint disease. We propose to develop inhibitors of G-CSF as a novel form of anti-cytokine therapy for inflammatory joint disorders, such as rheumatoid arthritis.Read moreRead less