Novel pharmacological agents to target stroke-induced brain injury. There is a looming stroke epidemic in Australia. 72% of Australian stroke sufferers are over the age of 65 and whereas in 1997 only 12% of Australians were in that age group, by 2030 that number will have increased to 23%. There is an urgent need for novel therapies. This project will aid the development of a novel anti-stroke therapy.
Enhancing Erythropoietin Therapy In Ischaemia-reperfusion Injury Of Heart And Kidney
Funder
National Health and Medical Research Council
Funding Amount
$361,021.00
Summary
Heart attacks and kidney disease from a lack of blood flow are common causes of morbidity and have poor treatment options. Erythropoietin (epo) is a useful new treatment, but there remain some caveats to its use in humans: eg. it may cause excessive scarring during repair. Use of epo with an anti-inflammatory drug may decrease scarring and provide benefit to long-term health. We plan to carefully define the biomolecular pathways of injury and repair, to better plan this therapy for human use.
Urotensin-II In Human Heart: Investigation Of Mechanisms Involved In Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$255,990.00
Summary
The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our finding ....The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our findings indicate that urotensin-II is the most potent heart stimulator identified to date. In patients with heart failure, short term stimulation of heart contraction is beneficial, supplying the heart and other organs with vital oxygen and nutrients. However, in the long term excessive stimulation causes worsening of the patients condition. Very little is currently known about the way in which urotensin-II alters heart function. The goal of our study is to understand the mechanism involved in urotensin-II mediated effects on the heart. This will involve identifying the location of urotensin-II and its receptors in the heart, and determining what signalling changes occur after the interaction of urotensin-II with its receptors. Urotensin-II must first be cleaved from a larger drug. We will determine where in the heart this cleavage occurs and whether the process is crucial to the ability of urotensin-II to stimulate contraction of the heart. Since stimulators of heart contraction are detrimental to patients with heart failure in the long term, we will determine whether these patients have more urotensin-II in their blood than patients who do not have heart failure. If the levels of urotensin-II are higher in heart failure patients, it may indicate a need to interfere with the interaction of urotensin-II with its receptors.Read moreRead less
Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test th ....Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test the efficacy of three proteins as anti-bleeding agents and investigate several other novel components. The ultimate outcome will be the development of novel drugs that will have application in the treatment of human disorders. Read moreRead less
An Implementation Trial Of A Telephone-based Care Management Program For Patients Following Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$641,656.00
Summary
We are trialling the implementation of an innovative telephone-delivered program for managing people who have had a heart attack. Cardiac rehabilitation programs are generally based in hospitals in Australia and people have to be able to attend the programs when they are offered. Even though such programs have been shown to be very effective in improving outcomes after a heart attack, at least 85% of Australians after a heart attack are either unable to access and-or unable to attend such progra ....We are trialling the implementation of an innovative telephone-delivered program for managing people who have had a heart attack. Cardiac rehabilitation programs are generally based in hospitals in Australia and people have to be able to attend the programs when they are offered. Even though such programs have been shown to be very effective in improving outcomes after a heart attack, at least 85% of Australians after a heart attack are either unable to access and-or unable to attend such programs due to transport and many other barriers. So, there is an urgent need to identify new, effective, and affordable ways of delivering cardiac rehabilitation programs to people after a heart attack. The proposed telephone-delivered program will be particularly appropriate for disadvantaged people, such as those living in rural and remote areas as well as Indigenous Australians, who do not currently have access to hospital-based cardiac rehabilitation programs. People who have had a heart attack will be recruited from three of Brisbane's largest public teaching hospitals, and will then be randomly assigned to the telephone-delivered cardiac rehabilitation program (Care Management Intervention group) or to a control or Usual Care group. The Care Management Intervention group will receive regular telephone calls from a highly qualified 'Care Manager' based at the renowned National Heart Foundation of Australia telephone support service, 'Heartline'. The Care Manager will help people to manage their heart condition and prevent the reoccurrence of further heart problems. People will also be encouraged to make necessary lifestyle and behavioural changes with the assistance of the Care Manager and some Heart Foundation educational and interactive resources to record their progress. We expect that the program or Care Management Intervention group will have better health outcomes than the control or Usual Care group at 6 and 12 months follow up.Read moreRead less
Transdermal penetration of corticosteroids in the dog. Topical application of corticosteroids enhances drug concentration and effectiveness in the treatment of skin diseases. Most topical corticosteroid preparations have been developed for human use and are poorly efficacious or promote a high incidence of adverse effects in dogs. This project will characterize corticosteroid penetration through canine skin to permit the development of suitable topical formulations to more effectively control ....Transdermal penetration of corticosteroids in the dog. Topical application of corticosteroids enhances drug concentration and effectiveness in the treatment of skin diseases. Most topical corticosteroid preparations have been developed for human use and are poorly efficacious or promote a high incidence of adverse effects in dogs. This project will characterize corticosteroid penetration through canine skin to permit the development of suitable topical formulations to more effectively control skin diseases in the dog. Skin diseases are a significant problem in veterinary science and this project will not only provide an effective therapeutic option, but also reduce animal (and client) distress when suffering skin disease and/or adverse effects from traditional therapy.Read moreRead less
Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepress ....Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepressant drugs and to the design of drugs to prevent the effects of cocaine.Read moreRead less
Pharmacological modification of retinal and visual function and relation to control of refractive error. Myopia (short-sightedness) affects many hundreds of millions of people worldwide and can lead to blindness. Drug treatments that prevent myopia are being developed, however there is no efficient way of determining who is at risk of myopia or who will benefit from these treatments. This fundamental research project will determine the retinal and visual effects of pharmacologic agents that inhi ....Pharmacological modification of retinal and visual function and relation to control of refractive error. Myopia (short-sightedness) affects many hundreds of millions of people worldwide and can lead to blindness. Drug treatments that prevent myopia are being developed, however there is no efficient way of determining who is at risk of myopia or who will benefit from these treatments. This fundamental research project will determine the retinal and visual effects of pharmacologic agents that inhibit myopia, with the aim of determining an ocular measure that is related to myopia, which is altered by drugs that are known to slow myopia progression, and that could be used as an indication of an agent's likely effectiveness.Read moreRead less
The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper u ....The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper understanding of how physiology and medicines work. The project expects to expand fundamental understanding of signal transmission at this receptor class. This project will deliver benefits including expanded basic knowledge and a contribution to future improvements in drug development.Read moreRead less
Probing norepinephrine transporter (NET) structure-function. More selective drugs are needed to improve the treatment of a range of diseases including pain, depression and anxiety. This project will apply advanced molecular pharmacology approaches to better understand how the norepinephrine transporter functions and where small molecules and conotoxins bind to inhibit its activity.