Mitochondrial Damage Following Fetal Hypoxia Or Birth Asphyxia: Using Creatine To Preserve Mitochondrial Function
Funder
National Health and Medical Research Council
Funding Amount
$838,726.00
Summary
There is a need for a therapy that can be given before a mother gives birth to protect the baby should ‘oxygen starvation’ threaten the baby’s brain and other organs such as the heart, kidney, lungs, and the ability to breathe properly. We are suggesting that an increased intake of creatine is a very effective treatment against this threat, and its proven safety and ease of use recommends it for wide application, particularly in countries where the access to medical resources is poor.
Radiotherapy Treatment For Prostate Cancer - A Change In Practice Based On Direct Evidence For Targeting And Toxicity Effects Using Real Outcomes Data
Funder
National Health and Medical Research Council
Funding Amount
$555,129.00
Summary
Radiotherapy for prostate cancer treatment will be more effective when we have better knowledge of what patient anatomy needs to be targeted, and what needs to be avoided. This project will combine data collected during a large Australasian prostate cancer radiotherapy trial, ‘RADAR’, with data collected using new patient imaging methods to determine how patient anatomy impacts on the effectiveness of their treatment and the side-effects they experience.
Understanding Mitochondrial DNA Segregation And Transmission.
Funder
National Health and Medical Research Council
Funding Amount
$512,449.00
Summary
We inherit our mitochondrial DNA from our mothers. Mutations to mitochondrial DNA can give rise to severely debilitating diseases that can be passed from one generation to the next. The aims of this application are to understand how mutant mitochondrial DNA is selected for; when it affects energy production during development; and to ensure that certain reproductive strategies do not result in the adverse transmission of mitochondrial DNA that will affect subsequent generations.
Understanding The Pathogenesis Of Mitochondrial Disease Using IPS Cells
Funder
National Health and Medical Research Council
Funding Amount
$640,372.00
Summary
Induced pluripotent stem (iPS) cells are stem cells derived from adult skin cells that can be converted into cell types such as neurons. iPS cells offer great promise in understanding and treating inherited disorders. However, there are concerns that the “epigenetic memory” of iPS cells has not been completely erased, which may limit the utility of iPS cells. We will evaluate and validate the use of iPS technology in mouse and human models of inherited disorders affecting energy generation.
Metabolic And Molecular Basis Of Embryo Signalling
Funder
National Health and Medical Research Council
Funding Amount
$409,836.00
Summary
Cells in the body are powered by mitochondria that essentially generate the energy required for development. This grant will determine how the environment affects the mitochondria in the developing embryo and determine the impacts to the embryo and pregnancy if a mitochondria is partially shut down.
Antimalarial Drugs In Pregnancy: Preclinical And Clinical Studies Of Conventional And Novel Agents
Funder
National Health and Medical Research Council
Funding Amount
$470,115.00
Summary
Women in malaria-endemic areas such as coastal PNG are at high risk of malaria in pregnancy. To prevent the substantially increased malaria-associated morbidity and mortality in mother and child, and because even asymptomatic infections can be deleterious, there has been a move to giving antimalarial drugs regularly during pregnancy regardless of the mother's clinical or parasitological status. In poor tropical countries, such treatment usually comprises safe and inexpensive agents such as chlor ....Women in malaria-endemic areas such as coastal PNG are at high risk of malaria in pregnancy. To prevent the substantially increased malaria-associated morbidity and mortality in mother and child, and because even asymptomatic infections can be deleterious, there has been a move to giving antimalarial drugs regularly during pregnancy regardless of the mother's clinical or parasitological status. In poor tropical countries, such treatment usually comprises safe and inexpensive agents such as chloroquine and Fansidar. There are two main issues with this approach. First, the efficacy of such conventional agents is waning and this increases the risk of break-through malaria. Second, there are few data on how the drugs are handled in pregnancy on which to base recommendations for treatment. We plan to collect information on the disposition and effectiveness of chloroquine and Fansidar in women with malaria in pregnancy in PNG that should allow a critical appraisal of the usefulness of current regimens in PNG and in other tropical countries where parasite resistance to these agents is emerging. Artemisinin combination therapy (ACT) in the form of a novel artemisinin drug and a longer-acting partner has been suggested as the most promising alternative therapy for malaria in pregnancy if conventional drugs fail. We plan to assess the safety of a leading ACT formulation, namely dihydroartemisinin and the chloroquine-like drug piperaquine (DHA-PQ), in animals before extending our studies to women with malaria in PNG. These latter studies will allow an evaluation of the safety and efficacy of DHA-PQ as novel therapy for malaria in pregnancy in PNG and other tropical countries.Read moreRead less
Improving Oocyte Mitochondrial DNA Copy Number To Enhance Female Reproductive Capacity.
Funder
National Health and Medical Research Council
Funding Amount
$670,867.00
Summary
Eggs with too few copies of mitochondrial DNA either fail to fertilise or arrest during early development. By supplementing eggs with mitochondrial DNA, we have been able to enhance embryo quality and gene expression profiles. By breeding the offspring derived from eggs given mitochondrial supplementation, we will determine if they and their progeny meet normal developmental milestones, regulate the transmission of mitochondrial DNA appropriately, and are healthy and fertile.
Unravelling The Mechanism Of MHC Class-I Associated Drug Hypersensitivities
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Some drugs cause adverse reactions that are life threatening. We think these reactions are mediated by killer T cells as they are genetically controlled by immune response genes that normally guide immunity to microbes. We will study immune reactions to the drug abacavir, used to treat HIV (AIDS); allopurinol used to prevent gout and carbamazepine, used to treat epilepsy. The study may also help devise better treatments for patients who experience severe forms of these reactions.
From Pathogenesis To Therapeutics: Targeting Two Signalling Pathways As A Therapeutic Strategy To Treat Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$499,048.00
Summary
Preeclampsia is a serious complication of pregnancy that claims the lives of thousands of mothers and babies each year. There is no efficacious medical treatment besides delivery of the baby and placenta. Our lack of therapeutics is largely a result of our poor understanding of the disease. In this application we plan to thoroughly characterise two pathways we believe responsible for preeclampsia, effectively identifying many points at which new therapies could be targeted.
Understanding The Metabolic Consequences Of Impaired AMPKa2 And NNOS� In Skeletal Muscle: Implications For The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$575,527.00
Summary
The inability of muscle to utilise sugar from the blood is a major problem that contributes to obesity and Type 2 diabetes. Since the number of people with these diseases will at least double by 2030, we need to find out what causes this problem. We will examine whether two muscle proteins that are impaired in obesity and Type 2 diabetes are also responsible for impaired sugar utilisation. We think that increasing these muscle proteins will fix the _sugar problem�, and remedy these diseases.