Can Decision Analytic Modelling Promote Clinical Translation Of Personalised Medicine Markers For Oncology Drugs?
Funder
National Health and Medical Research Council
Funding Amount
$69,893.00
Summary
Personalised medicine is an approach that has great potential to improve healthcare. There has been limited success to date, however, in utilising proposed tests in the clinical. It is proposed that use of mathematical models early in the development of personalised medicine tests will allow early understanding of the value that the test will have for patients and society. Such insight will help build a strong case to undertake the research required before personalised medicine can be more widel ....Personalised medicine is an approach that has great potential to improve healthcare. There has been limited success to date, however, in utilising proposed tests in the clinical. It is proposed that use of mathematical models early in the development of personalised medicine tests will allow early understanding of the value that the test will have for patients and society. Such insight will help build a strong case to undertake the research required before personalised medicine can be more widely used to improve treatment for cancer.Read moreRead less
Gene Expression And DNA Methylation In Barrett's Oesophagus And Oesophageal Adenocarcinoma
Funder
National Health and Medical Research Council
Funding Amount
$383,655.00
Summary
The oesophagus (gullet) is the tube through which food and drinks pass from the mouth to the stomach. In Barrett's oesophagus, the normal lining of the lower oesophagus is replaced by an abnormal type of lining called intestinal metaplasia as a result of severe gastroesophageal reflux. Gastroesophageal reflux is one of the most common of all diseases, affecting up to a quarter of all adults, and Barrett's oesophagus itself occurs in 0.5 - 1% of the adult population. In a minority of patients wit ....The oesophagus (gullet) is the tube through which food and drinks pass from the mouth to the stomach. In Barrett's oesophagus, the normal lining of the lower oesophagus is replaced by an abnormal type of lining called intestinal metaplasia as a result of severe gastroesophageal reflux. Gastroesophageal reflux is one of the most common of all diseases, affecting up to a quarter of all adults, and Barrett's oesophagus itself occurs in 0.5 - 1% of the adult population. In a minority of patients with Barrett's oesophagus, further abnormalities in the cells lining the lower oesophagus occur, leading to dysplasia and adenocarcinoma (glandular cell type cancer). This project will provide the first comprehensive map of two of the most important genetic mechanisms (gene expression and DNA methylation) by which Barrett's oesophagus evolves into Barrett's dysplasia and adenocarcinoma. The specimens studied in this project differ from previous studies in that they are taken from the same patients at different times, as these patients' Barrett's oesophagus either remains stable or progresses to worse disease. Essentially all the known human genes will be studied and the relevance of genes identified as important will be confirmed using highly accurate methods. With this information, it may be possible to develop genetic tests that can predict which patients are at risk of developing worse disease including cancer. In other parts of this project, genes which influence the likelihood of survival for patients with oesophageal adenocarcinoma will be identified, a simple test to more accurately identify patients with cancer spread to lymph nodes may be developed, and a blood test to detect oesophageal adenocarcinoma will be tested.Read moreRead less
This study aims to identify naturally occurring genetic variations between men which modify the impact of testosterone, the major male hormone, on men's health and medical care. This study will examine new factors which determine how much any particular man may gain benefit from testosterone exposure such as in muscle and bone development as well as suffer detrimental effects on cardiovascular and prostate diseases. This may clarify some new aspects of how men's health is determined as well as d ....This study aims to identify naturally occurring genetic variations between men which modify the impact of testosterone, the major male hormone, on men's health and medical care. This study will examine new factors which determine how much any particular man may gain benefit from testosterone exposure such as in muscle and bone development as well as suffer detrimental effects on cardiovascular and prostate diseases. This may clarify some new aspects of how men's health is determined as well as developing new, customized medical treatments for men.Read moreRead less
Pharmacogenetic Investigations Of Glutathione Transferases
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
Members of the family of enzymes known as glutathione transferases are known to be responsible for the metabolism and detoxification of a wide range of compounds including therapeutic drugs and cancer causing chemicals. Genetic variation in an individual's compliment of glutathione transferases can alter their response to drug treatment or their susceptibility to cancer. This study will investigate (1)the genetic mechanisms that alter the production of glutathione transferases, (2) the character ....Members of the family of enzymes known as glutathione transferases are known to be responsible for the metabolism and detoxification of a wide range of compounds including therapeutic drugs and cancer causing chemicals. Genetic variation in an individual's compliment of glutathione transferases can alter their response to drug treatment or their susceptibility to cancer. This study will investigate (1)the genetic mechanisms that alter the production of glutathione transferases, (2) the characteristics of a new class of glutathione transferases and (3) the role of glutathione transferase A4 in protecting against disorders such as atherosclerosis and Parkinson's disease.Read moreRead less
Clozapine Toxicity: Role Of Pharmacogenetic Variation In CYP Enzymes And Bioactivation Mechanisms In Patient Neutrophils
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
The treatment of mental disorders such as schizophrenia involves the administration of potent drug combinations to patients. Some individuals, however, do not respond to commonly-used antipsychotic drugs and their condition only improves with a unique drug called clozapine. The major problem with clozapine is its toxicity toward blood cells, heart and other organs. All people who receive clozapine must be monitored closely, especially in the first 3-4 months after starting therapy. Several new d ....The treatment of mental disorders such as schizophrenia involves the administration of potent drug combinations to patients. Some individuals, however, do not respond to commonly-used antipsychotic drugs and their condition only improves with a unique drug called clozapine. The major problem with clozapine is its toxicity toward blood cells, heart and other organs. All people who receive clozapine must be monitored closely, especially in the first 3-4 months after starting therapy. Several new drugs have been suggested to be safer versions of clozapine but these are all ineffective. Clozapine is the only agent that is effective in people who do not respond to the other drugs used to treat schizophrenia. Thus, clozapine toxicity, which necessitates discontinuation of the drug, is a devastating outcome because there is no alternative treatment that is available. Another significant problem with clozapine is that its rate of removal from the body is slowed down by many other drugs that are used concurrently. The problems with clozapine occur in some but not all individuals. This suggests that the patient's genetic makeup and their exposure to drugs and environmental agents determine the incidence of toxicity. The present project looks at how clozapine is removed from the body and how it is converted into a toxic product that damages cells. These processes will be examined, with emphasis on differences between individual patients, and strategies to protect cells from damage from the toxic derivative will be tested. Corresponding studies will be done in patients who are receiving clozapine as treatment for psychoses. We will be able to compare experimental and clinical findings in order to identify those patients who appear to be at risk. This will be possible before the toxic effects occur and will help us to identify subjects in whom the drug should only be used with great care. We may also devise strategies that will minimise the incidence of toxicity.Read moreRead less
A Trial Of Therapeutic Drug Monitoring In Methadone Maintenance Treatment
Funder
National Health and Medical Research Council
Funding Amount
$542,025.00
Summary
Heroin addiction is an established and increasing problem in developed countries and in many developing nations. Although there have been several new treatments for heroin addiction, methadone maintenance remains the most effective way to minimize the harms associated with heroin addiction. The current research proposal seeks to test a new approach to setting of methadone dose, using monitoring of methadone blood levels, effects and side-effects in determining when to increase doses, and when to ....Heroin addiction is an established and increasing problem in developed countries and in many developing nations. Although there have been several new treatments for heroin addiction, methadone maintenance remains the most effective way to minimize the harms associated with heroin addiction. The current research proposal seeks to test a new approach to setting of methadone dose, using monitoring of methadone blood levels, effects and side-effects in determining when to increase doses, and when to switch to alternative therapies. This provides an objective method of planning treatment that focuses on suppressing heroin use. The potential subjects of the study are the 50% of patients who continue to use heroin regularly during treatment. All will undergo assessment involving measurement of blood levels of methadone, testing of effects and side-effects of methadone, and monitoring of safety. Half will be randomly allocated to usual care, and half to therapeutic drug monitoring, with dose adjustments according to the results of testing. At 3 and 6 months all subjects will undergo repeat test sessions. It is hypothesized that those in the experimental group will be using less heroin (confirmed by hair testing). It is expected that the study will also identify a small group of subjects with genetically different opioid receptors, who will require very high doses of methadone to be stabilized. The study will allow a detailed analysis of how best to monitor dose adequacy; the relationship between withdrawal symptoms, methadone blood levels, and heroin use, and will provide the first clear investigation of the relationship between changes in methadone blood concentration and certain potentially dangerous changes in the electrical activity of the heart. The intended outcome of this research project is a model for a higher standard methadone program that is more effective in reducing the problems of heroin use in our community.Read moreRead less