Understanding The Mechanisms Of Functionally Selective Antipsychotic Drugs: Implications For New Generation Antipsychotic Drugs
Funder
National Health and Medical Research Council
Funding Amount
$371,745.00
Summary
Schizophrenia is a chronic and devastating disease that ranks among the top 10 disabilities in developed countries. It places a significant burden on the Australian health system, costing about $1.5 billion each year. This project aims to reveal the mechanisms of new functionally selective antipsychotic drugs, which achieve an excellent therapeutic efficacy with low side-effects. Understanding these mechanisms will provide novel directions for the design of new generation antipsychotic drugs.
Development Of A Multi-faceted Diagnostic And Predictive Tool To Characterise Type Of Diabetes, Therapeutic Progression And Outcome
Funder
National Health and Medical Research Council
Funding Amount
$352,550.00
Summary
Diabetes is diagnosed using clinical assessment complemented by a few selected basic conventional laboratory tests. We plan to determine, in a representative community-based sample of Australian with diabetes, whether additional knowledge of genetic markers, diabetes-related antibody levels and tests of insulin secretory capacity adds to diagnosis of diabetes type, prediction of therapeutic progression over time, complications and death.
Mechanisms Of Cartilage Destruction And The Effects Of Treatment In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$239,830.00
Summary
Rheumatoid arthritis occurs in 1-3% of the population. It is associated with damage to joints causing pain and dificulty with mobility. There are several treatments for rheumatoid arthritis, none of which completely prevents this damage. This study looks at joint tissue and the ways in which damage occurs. It tries to understand why treatment works in some patients and not others. By doing this, the best ways of stopping joint damage will be determined. The study will also tell us the best ways ....Rheumatoid arthritis occurs in 1-3% of the population. It is associated with damage to joints causing pain and dificulty with mobility. There are several treatments for rheumatoid arthritis, none of which completely prevents this damage. This study looks at joint tissue and the ways in which damage occurs. It tries to understand why treatment works in some patients and not others. By doing this, the best ways of stopping joint damage will be determined. The study will also tell us the best ways of looking at whether treatment is working before joint damage occurs.Read moreRead less
Diet As A Therapeutic Target In Depression: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$498,564.00
Summary
Depression is predicted to become the second-most common cause of disability in the world by 2020. While there is now compelling new evidence to suggest that diet plays an important role in the risk for and the genesis of depression, there are no existing data regarding the impact of dietary improvement on existing depressive illness. The aim of the proposed study is to answer the critically important and frequently asked question "If I improve my diet, will my mental health improve?"
Opioids As A New Therapy For Inflammatory Arthritis: Immunopharmacological Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$406,527.00
Summary
Arthritis is a chronic inflammatory disorder characterized by joint pain, swelling and stiffness. In fact, 69% of patients present with radiographic erosions and joint space narrowing during the first three years of the disease and it is insufficiently appreciated that patients with rheumatoid arthritis may have a 5-year mortality similar to patients with cardiovascular or neoplastic disease. Prevention of disability and death is the ultimate goal of treatment. However, no cure is yet available. ....Arthritis is a chronic inflammatory disorder characterized by joint pain, swelling and stiffness. In fact, 69% of patients present with radiographic erosions and joint space narrowing during the first three years of the disease and it is insufficiently appreciated that patients with rheumatoid arthritis may have a 5-year mortality similar to patients with cardiovascular or neoplastic disease. Prevention of disability and death is the ultimate goal of treatment. However, no cure is yet available. Instead, current treatment is aimed at relieving symptoms and improving functional performance. There is now a growing recognition that patients with rheumatoid arthritis require more agressive treatment early in the disease, before the development of erosions and deformity. My work has shown for the first time that opioid drugs that act via kappa (k) receptors in the periphery are able to ameliorate the incidence and severity of disease symptoms in rat adjuvant arthritis. Histological and radiological analysis reveals a significant, beneficial effect on joint pathology. The present proposal seeks to build upon this basic information gained in rats into the anti-inflammatory mechanisms of opioid action. I will now apply my expertise to extend this research in animals to human tissues. I am able to combine multiple techniques to carry out a systematic and rigorous study on human synovium from arthritis patients. This work aims to find out why opioids have anti-arthritic actions and might potentially lead to potent, less toxic and less expensive new therapies for arthritis and increase our understanding of the pathogenesis of arthritis.Read moreRead less
Heat Shock Transcription Factors In Bone Remodeling And Disease
Funder
National Health and Medical Research Council
Funding Amount
$480,427.00
Summary
The denisity of bone is finely balaned and required for a healthy lifestyle. During times of disease, damage or drug treatments the bone can be compromised, often decreasing in density and becoming fragile. This often leads to fractures, pain and a poor quality of life. This proposal seeks to investigate whether stress insults to bones plays a role in the loss of bone. This will provide new insights into bone loss during disease and lead to novel treatment strategies.
Measuring Adverse Events: Development Of A Patient-Centred Adverse Event Reporting Tool (PAET)
Funder
National Health and Medical Research Council
Funding Amount
$454,721.00
Summary
The decision to treat a patient depends on knowing whether the treatment does more good than harm. If it is likely that the treatment will work as well as or better than other treatments and will have minimal associated risks, then that treatment would be recommended unless unavailable or prohibited by cost. Given two equally effective treatments the one with fewer side effects and greater tolerability would be preferred by all. In the process of acquiring knowledge on treatment benefit and trea ....The decision to treat a patient depends on knowing whether the treatment does more good than harm. If it is likely that the treatment will work as well as or better than other treatments and will have minimal associated risks, then that treatment would be recommended unless unavailable or prohibited by cost. Given two equally effective treatments the one with fewer side effects and greater tolerability would be preferred by all. In the process of acquiring knowledge on treatment benefit and treatment harm we rely on evidence from clinical trials. However, the evaluation of benefit versus harm is not symmetric in this setting. Much more effort (e.g. study design, study power, standardisation of efficacy outcome measures) goes into the assessment of whether a treatment works and rather than its potential harm, as measured by adverse events. Adverse event ascertainment and reporting is poorly standardised . There is no standardised measurement process that elicits adverse event information. There is no standardised method for quantifying adverse event information into an index or profile scores equivalent to instruments developed to measure health status, quality of life and other benefits of treatment. Developing astandardised Patient-centred Adverse Event Questionnaire will benefit multiple stakeholders. For Patients: An easy to understand summary measure of treatment harm aids patient understanding of the benefit versus risk. For Doctors, allied health professionals: The Questionnaire includes drug profiles, to align a drug profile with an individual patient's clinical profile. This leads to better patient care. In health policy: All of the above has flow-on effects for policy. Better adverse event data will facilitate information and understanding generally of risks of treatments, risk-benefits of treatments, and cost-effectiveness of management strategies.Read moreRead less
Molecular Imaging Of Brain Tumour Therapeutic Efficacy
Funder
National Health and Medical Research Council
Funding Amount
$412,200.00
Summary
The prognosis for malignant brain tumour patients that do not respond to intial treatment strategies is very poor. The fact that many of these patients patients will not survive longer than 12 months post diagnosis underscores the need to make treatment management decisions in a timely manner. This project seeks to develop and validate non-invasive early molecular imaging biomarkers that can quantify treatment efficacy months before traditional measures of efficacy are valid.
MECHANISMS OF PATHOLOGY AND NEW THERAPEUTIC OPTIONS FOR GAUCHER DISEASE AND OTHER LIPIDOSES
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
The sphingolipidoses are a subgroup of the more than 45 genetic disorders known collectively as lysosomal storage disorders (LSD). As a result of the deficiency of specific enzymes or proteins involved in the breakdown of sphingolipids (fats), there is an accumulation of this material in affected cells. These diseases can affect liver, spleen, kidney, bone and the central nervous system. Gaucher disease is the prototype for the sphingolipidoses and, in this project, we will use this disease as a ....The sphingolipidoses are a subgroup of the more than 45 genetic disorders known collectively as lysosomal storage disorders (LSD). As a result of the deficiency of specific enzymes or proteins involved in the breakdown of sphingolipids (fats), there is an accumulation of this material in affected cells. These diseases can affect liver, spleen, kidney, bone and the central nervous system. Gaucher disease is the prototype for the sphingolipidoses and, in this project, we will use this disease as a model for this group of disorders. Gaucher disease in the most prevalent LSD with an incidence of 1:56,00 births, worldwide there are approximately 2300 affected individuals born each year. Enzyme replacement therapy (ERT) for Gaucher disease has been successful in the treatment of the non-neuropathic form of the disease. However ERT is expensive ($200,000-400,000 pa). There are approximately 50 Australian patients undergoing ERT at a cost of at least $10 million per annum. However, due to the high cost of treatment, many people do not qualify for ERT, despite having serious medical problems. Worldwide, there are approximately 4000 people currently receiving ERT for Gaucher disease at a total drug cost of over $1.0 billion pa. However, based on birth rates and life expectancies there are over 80,000 Gaucher patients in the world. With the current cost of ERT it is likely that over 90% of these will never receive ERT. If therapy is to be made available for the majority of affected individuals, cheaper alternatives will be required. In this project we will use cellular models of Gaucher disease to study the processes leading to the disease and to develop alternative, cheaper therapies for this disease and other types of sphingolipidoses, for which no therapies currently exist.Read moreRead less
Novel Therapeutic Strategies To Reduce The Burden Of Chronic Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$4,928,323.00
Summary
The broad aims of the Program are to develop novel strategies in the prevention and treatment of chronic heart failure. This will involve investigating new targets for pharmacological therapies, evaluating whether common co-morbid disease states such as diabetes alter the efficacy of these therapies and investigating the role of stem-cell therapy in this setting. The Program will also evaluate the contribution of non-heart failure drugs to the burden of heart failure, determine the impact of rur ....The broad aims of the Program are to develop novel strategies in the prevention and treatment of chronic heart failure. This will involve investigating new targets for pharmacological therapies, evaluating whether common co-morbid disease states such as diabetes alter the efficacy of these therapies and investigating the role of stem-cell therapy in this setting. The Program will also evaluate the contribution of non-heart failure drugs to the burden of heart failure, determine the impact of rurality on prescribing for this condition and explore systems of optimising delivery of best practice to the community. This research formalises the existing collaborative efforts of a team of investigators that span all aspects of research into the therapeutics of CHF from basic laboratory research to evaluation of patients in clinical trials and public health translational aspects of this condition. The Chief Investigators and Principal Investigators have an existing successful research collaboration which will be greatly expanded via Program.Read moreRead less