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
A type of white blood cell, the macrophage, is a key player in determining the chronicity of inflammatory conditions such as rheumatoid arthritis, atherosclerosis, psoriasis, nephritis, multiple sclerosis etc. Two particular proteins can control macrophage development and functions, both under normal conditions and during inflammation. The project aims to understand this control. More rational ways to suppress inflammation due to aberrant macrophage function should result.
Towards A Rational Strategy For Osteoarthritis Therapy
Funder
National Health and Medical Research Council
Funding Amount
$945,993.00
Summary
Osteoarthritis is the most common form of arthritis, causing disability and chronic pain, for which there are no adequate treatments. Our laboratory has shown that a particular protein is involved in inflammatory arthritis and pain. Blocking this protein in patients with rheumatoid arthritis is showing success. In this project we will carry out some preclinical studies to determine whether blockade of this protein may also be a therapeutic target for osteoarthritis pain and disease.
GM-CSF Regulation Of Preimplantation Embryo Development
Funder
National Health and Medical Research Council
Funding Amount
$481,320.00
Summary
Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be ov ....Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.Read moreRead less
The study of growth factors essential in normal kidney and lung development allows for the advancement of innovative therapies to promote postnatal growth and repair. A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of colony stimulating factor (CSF-1), a growth factor important for fetal growth during pregnancy. We have evidence that CSF-1 therapy can promote lungs to continue development and maturation aft ....The study of growth factors essential in normal kidney and lung development allows for the advancement of innovative therapies to promote postnatal growth and repair. A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of colony stimulating factor (CSF-1), a growth factor important for fetal growth during pregnancy. We have evidence that CSF-1 therapy can promote lungs to continue development and maturation after birth.Read moreRead less
A type of white blood cell, the macrophage, is a key player in determining the chronicity of inflammatory conditions such as rheumatoid arthritis, atherosclerosis, psoriasis, nephritis, multiple sclerosis etc. Two particular proteins can control macrophage development and functions, both under normal conditions and during inflammation. The project aims to understand this control. More rational ways to suppress inflammation due to aberrant macrophage function should result.