Novel Cellular Trafficking Mechanisms For The Drug Influx Transporter, Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in indivi ....Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in individuals.Read moreRead less
Improving The Use Of Chemotherapy By Targeting The Inflammatory Response
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
Patient differences in clearance of anti-cancer drugs have a major impact on the success of chemotherapy. Benefit is lost if the drug is cleared too rapidly, while slow elimination causes toxicity. We will use well characterised mouse models that mirror the human situation to study the causes and effects of reduced drug metabolism in cancer. The data will guide future human studies that will result in improved diagnostic and therapeutic interventions to improve the tolerance of chemotherapy.
Quantitative In Vitro-in Vivo Extrapolation: Realising The Promise
Funder
National Health and Medical Research Council
Funding Amount
$529,509.00
Summary
Most drugs are 'broken down', or metabolised, in the body by enzymes which are located mainly in liver. Knowing the efficiency of drug metabolism in patients is important for the discovery of new drugs and for the rational use of established drugs. This project will develop in vitro, or test-tube, approaches that predict how well a drug is metabolised in humans and whether it will interact with coadminsitered drugs. In turn, this allows prediction of drug dosage and frequency of administration.
Enhancing Peripheral Clearance Of Beta Amyloid As A Treatment For Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$548,681.00
Summary
Amyloid-beta (abeta) accumulation in the brain is a key step in the development of Alzheimer's disease, with potential therapies focusing on its clearance. Compounds that bind abeta in blood have been shown to alter brain abeta levels. We will assess the efficacy of a novel abeta-binding peptide to promote peripheral clearance of brain-derived abeta in a mouse model of AD. Such a drug would be effective in sporadic AD, where the efflux transport, clearance and degradation systems are defective.
Pharmacokinetic And Pharmacodynamic Studies Of The Newer Immunosuppressants
Funder
National Health and Medical Research Council
Funding Amount
$406,650.00
Summary
After an organ transplant (such as a liver or kidney transplant), people need to take medicines continually to stop their immune systems from rejecting their new organ. This treatment with immunosuppressant drugs is vital for long-term success of the graft. These drugs are designed to prevent rejection in patients who have received organ transplants (e.g. kidney, liver) and are also being used to treat a variety of autoimmune diseases, including rheumatoid arthritis. However, too many people are ....After an organ transplant (such as a liver or kidney transplant), people need to take medicines continually to stop their immune systems from rejecting their new organ. This treatment with immunosuppressant drugs is vital for long-term success of the graft. These drugs are designed to prevent rejection in patients who have received organ transplants (e.g. kidney, liver) and are also being used to treat a variety of autoimmune diseases, including rheumatoid arthritis. However, too many people are losing transplanted organs, or not achieving remission from their autoimmune diseases, or are experiencing significant illness and sometimes death from over immunosuppression (infection or side effects) because these drugs are not being used in the best way. The quality and duration of life of increasing numbers of Australians is being affected by lack of understanding and application of some basic principles about dosing regimens for these drugs. The aim of this project is to accurately define the best way to dose these newer immunosuppressant drugs in Australian populations, before they become more widely used .Read moreRead less