Development Of Modified IGF-binding Proteins As Novel Anti-cancer Chemotherapeutics
Funder
National Health and Medical Research Council
Funding Amount
$77,375.00
Summary
We propose to enhance the effectiveness of current anti-cancer treatments by co-administering a protein to sequester growth factors that promote the resistance of cancer cells to chemotherapy. We aim to achieve improved destruction of breast and colorectal cancers but with reduced adverse side effects. Our in vitro data show the effectiveness of this novel co-therapeutic which is a modified form of a natural carrier protein for these growth factors. This application seeks funding to enable proof ....We propose to enhance the effectiveness of current anti-cancer treatments by co-administering a protein to sequester growth factors that promote the resistance of cancer cells to chemotherapy. We aim to achieve improved destruction of breast and colorectal cancers but with reduced adverse side effects. Our in vitro data show the effectiveness of this novel co-therapeutic which is a modified form of a natural carrier protein for these growth factors. This application seeks funding to enable proof of concept in vivo in order to attract commercial funding for clinical trials.Read moreRead less
Pre-clinical Assessment Of Novel Growth Factor Complexes As A Topical Agent In The Treatment Of Deep
Funder
National Health and Medical Research Council
Funding Amount
$156,870.00
Summary
Healing of deep burns, unlike that of superficial injuries, often resolves with scarring. Scarring is reduced with rapid closure of burns. The CIs have discovered and patented novel growth factor complexes that stimulate the growth and migration of keratinocytes, cells derived from skin. Hence these complexes hold therapeutic potential for wounds that require rapid closure such as deep burns. This application will provide pre-clinical, proof-of-principle data to facilitate future patient trials.
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
Development Of Engineered Novel Growth Factors For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$410,439.00
Summary
Infertility comes at an enormous social and financial cost to Australian society. The aim of this proposal is to improve the success rate of an innovative technology that matures eggs in the laboratory and so eliminates the need for the hormones normally used in IVF. To achieve this a newly discovered egg-secreted protein first has to be produced in the laboratory.
Exploitation Of Unique Growth Factors To Develop New Products For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$132,525.00
Summary
Infertility comes at an enormous social and financial cost to Australian society; infertility is a major psychological burden on young couples and the technologies used to treat infertility, such as in vitro fertilisation (IVF), require expensive drugs to stimulate the ovary. The cost of these drugs to Medicare is expected to exceed $100 million p.a. over the next decade. A reproductive technology, which has always shown great potential to elevate some of this burden, is oocyte (egg) in vitro ma ....Infertility comes at an enormous social and financial cost to Australian society; infertility is a major psychological burden on young couples and the technologies used to treat infertility, such as in vitro fertilisation (IVF), require expensive drugs to stimulate the ovary. The cost of these drugs to Medicare is expected to exceed $100 million p.a. over the next decade. A reproductive technology, which has always shown great potential to elevate some of this burden, is oocyte (egg) in vitro maturation (IVM), which drastically reduces the use-cost of drugs and the stress to patients. However, oocyte IVM has been slow to live up to its potential and the technology is still not in widespread clinical practice, mainly due to disappointing success rates in women. We have been studying oocyte IVM in animals for many years, and have recently made a significant technological breakthrough, improving success rates by ~50%. In this field, a 50% increase in efficiency is substantial and has significant clinical and commercial application. Currently, we are the only group worldwide with this technology. Over the course of this 2-year project we will conduct follow-up experiments to refine this discovery and investigate the feasibility of using this approach to treat human infertility. We are already in negotiations with two medical device manufacturers to licence this technology. We expect that this project will lead to a series of products and technologies that will enter a clinical trial for the treatment of infertility within 2-3 years.Read moreRead less
Developing Novel Anti-cancer Agens By High Throughput Chemical Screens For Small Molcules That Modulate The Pro-survival
Funder
National Health and Medical Research Council
Funding Amount
$125,000.00
Summary
Cancer is the second commonest cause of deaths in our community. Unfortunately, treatment often fails or causes unwanted side effects. This proposal seeks to discover and develop a novel class of anti-cancer drugs that act by directly activating programmed cell death (apoptosis). The Bcl-2 proteins are key regulators of cell death and by exploiting knowledge about these prime targets for cancer therapy, we aim to discover drugs that are potentially of considerable medical and commercial value.
Therapeutic Strategies And Screening Methods For PKC Epsilon Antagonists In The Treatment Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$157,375.00
Summary
Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown ....Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown that an enzyme found in the pancreas becomes inappropriately activated under conditions of fat oversupply, and plays an important role in the development of defects in insulin release from the pancreas in response to glucose. Excitingly, we have also shown that inhibition of this enzyme can partly reverse these defects once they have been established. We now intend to further validate this enzyme as a drug target by determining the optimum dosing regimen for the treatment of type 2 diabetes in a mouse model, and testing whether this approach can be used in conjunction with previously-developed drugs which promote insulin action, to improve bood glucose handling better than either treatment alone. This would promote the enzyme as a therapeutic strategy in the treatment of Type 2 diabetes. We also plan to develop a high throuhput screen to identify novel inhibitors of the enzyme, which will further increase the attractiveness of the project to pharmaceutical companies, who are better able to implent full commercialization of our findings.Read moreRead less
Novel Methods For Promoting Organ Development And Growth
Funder
National Health and Medical Research Council
Funding Amount
$390,203.00
Summary
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). We have evidence that CSF-1 therapy can promote kidneys and lungs to continue development and maturation after birth. This exciting new finding allows for the application of CSF-1 therapy for both the treatment of premature babies and unborn babies with kidney defects.
Development Of Anti-metastatic And Tumour Targeting Reagents By Design Of Inhibitors To Specific Eph/ephrin Cell-cell
Funder
National Health and Medical Research Council
Funding Amount
$200,000.00
Summary
Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (E ....Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (Ephs) and their membrane-bound ephrin ligands are crucial mediators of cell adhesion and motility and are notably overexpressed in metastatic tumours rather than primary (benign) lesions5. Our laboratories were the first to identify EphA3 7, and one of the first to isolate its ligand, ephrin-A5. EphA3 was isolated from acute lymphoblastoid leukemia and malignant melanoma patients, where increasing expression levels correlate with metastatic progression. Soluble, non-clustered forms of Ephs and ephrins are effective inhibitors of Eph activity 3 and provide opportunities to generate specific drugs for cancer therapy. We now propose a research and development program for the development of EphA3-specific drugs and their production for pre-clinical and clinical evaluation for placement onto a national and international market.Read moreRead less
Stage II In The Development Of Eph/ephrin Based Tumor Targeting Reagents: Optimisation Of Drug Efficacy And Delivery
Funder
National Health and Medical Research Council
Funding Amount
$204,125.00
Summary
In the final stage of cancer, including melanoma, tumor cells gain the ability to spread, a process called metastasis. Altered communication between cancer and normal cells is one of the causes of this invasive characteristic. We have started the development of novel agents that target and modulate proteins on the cell surface that control these properties and are found in metastatic tumors. We propose to refine the targeting and killing properties of these agents for early clinical testing.