Causes Of Multiple Sclerosis: A Functional Genomics Approach
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Multiple sclerosis (MS) is a chronic disease that damages the brain and spinal cord and can cause, numbness, muscle weakness, difficulties with coordination and balance, problems with speech and swallowing, visual problems, fatigue and bladder and bowel difficulties. After a world-wide effort, a large number of multiple sclerosis genes have been localized in the human genome. This project examines three of these in detail aiming to identify exactly how they contribute to the risk of developing M ....Multiple sclerosis (MS) is a chronic disease that damages the brain and spinal cord and can cause, numbness, muscle weakness, difficulties with coordination and balance, problems with speech and swallowing, visual problems, fatigue and bladder and bowel difficulties. After a world-wide effort, a large number of multiple sclerosis genes have been localized in the human genome. This project examines three of these in detail aiming to identify exactly how they contribute to the risk of developing MSRead moreRead less
Orexin/Hypocretin Receptors In Self-Administration And Stress-Induced Reinstatement Of Ethanol Seeking
Funder
National Health and Medical Research Council
Funding Amount
$538,221.00
Summary
Orexin receptors are novel therapeutic targets implicated in alcohol use disorders. There is little known about how orexin receptors drive ethanol consumption and stress-induced reinstatement. This project provides a unique opportunity to determine the mechanism of action of orexin receptors in alcohol use disorders and devise novel therapeutic strategies to treat alcohol use disorders.
We need to think laterally to find effective treatments for people with dementia. Using relevant animal models and cutting-edge technology, my research investigates gene-environment interactions. In particular, my group is studying the pathophysiology of Huntington’s disease, a devastating progressive disorder with no current cure. By integrating my unique wide-ranging expertise and my extensive network of collaborators, I aim to explore mechanisms and to discover novel therapeutic strategies.
The Role Of Neuronal Nicotinic Receptor Subunits In The Self-Administration And Relapse To Alcohol Seeking:Treatments For Alcohol Dependence
Funder
National Health and Medical Research Council
Funding Amount
$531,787.00
Summary
The World Health Organization reports that alcohol causes almost two million deaths every year and results in physical disability or shortened life span for at least 58 million others. Despite the fact that addiction represents more than 40% of brain-related illnesses, there is a dearth of innovative treatments. The overall goal of my research is to develop more effective medications for the treatment of alcohol use disorder by targeting the neuronal nicotinic receptor subtypes that have been sp ....The World Health Organization reports that alcohol causes almost two million deaths every year and results in physical disability or shortened life span for at least 58 million others. Despite the fact that addiction represents more than 40% of brain-related illnesses, there is a dearth of innovative treatments. The overall goal of my research is to develop more effective medications for the treatment of alcohol use disorder by targeting the neuronal nicotinic receptor subtypes that have been specifically altered by heavy alcohol intake.Read moreRead less
Adult Stem Cell Transplantation Therapy In Parkinsonian Rat
Funder
National Health and Medical Research Council
Funding Amount
$526,517.00
Summary
Parkinson's disease is a progressive neurodegenerative disorder characterised by slowness of movement, muscle rigidity and tremor. It affects about 1% of the population at age 50 and 10% over age 80. Symptoms are caused by low levels of dopamine, a chemical in the brain that helps control movement. The symptoms increase in severity with time, leading to increasing difficulty in walking, speaking, writing, swallowing and sleeping and increasing the incidence of broken bones from falls. Parkinson' ....Parkinson's disease is a progressive neurodegenerative disorder characterised by slowness of movement, muscle rigidity and tremor. It affects about 1% of the population at age 50 and 10% over age 80. Symptoms are caused by low levels of dopamine, a chemical in the brain that helps control movement. The symptoms increase in severity with time, leading to increasing difficulty in walking, speaking, writing, swallowing and sleeping and increasing the incidence of broken bones from falls. Parkinson's disease is incurable but the symptoms can be controlled with medications that replace the lost dopamine. Medications become less effective as the disease progresses and there is need for new therapies. Worldwide the hunt is on to discover new cell transplantation therapies to replace the dopamine in the brain and to prevent degeneration of the still surviving dopamine cells. Although embryonic stem cells might be useful for such therapies, they raise the risk of tumour formation from the transplanted cells. This aim of this proposal is to test, in parkinsonian rat, a therapy in which adult stem cells from the patient are transplanted into their own brain to provide a new source of dopamine. We have discovered a new and unique source of adult stem cells, the sense organ of smell in the nose. Small samples can be taken through the nose and we can grow these adult stem cells from people of all ages, including people with Parkinson's disease. As adult stem cells they avoid the ethical issues associated with embryonic stem cell transplantation and as cells from the same patient, they are not rejected by the immune system. This is being tested in principle by a world-first clinical trial in which we are taking another cell type from the nose, growing it in the lab, and transplanting into the injured spinal cord in a search for a cure for paraplegia. This project takes the first steps to developing a new treatment for Parkinson's disease using a patient's own adult stem cells.Read moreRead less
IMPROVING STROKE OUTCOMES: NEW TARGETS AND THERAPIES
Funder
National Health and Medical Research Council
Funding Amount
$7,212,064.00
Summary
Previously we established a unique collaboration of researchers from the basic and clinical sciences.. The main aim of this ' vertically integrated ' model was to develop new therapies to improve stroke outcomes. We developed a system to identify ' off-the-shelf ' compounds which protect the brain after stroke onset. This involves data assimilation (meta-analysis) in a unique way, an approach which has attracted attention internationally. We are also completing an important clinical trial using ....Previously we established a unique collaboration of researchers from the basic and clinical sciences.. The main aim of this ' vertically integrated ' model was to develop new therapies to improve stroke outcomes. We developed a system to identify ' off-the-shelf ' compounds which protect the brain after stroke onset. This involves data assimilation (meta-analysis) in a unique way, an approach which has attracted attention internationally. We are also completing an important clinical trial using the clot dissolving agent tPA to extend the time during which the drug may be effective beyond the three-hours currently used. In the next phase of our program we plan to expand the basic science component to identify parts of brain cells (axons and dendrites) which may yield important information about new drugs to protect the brain. We will use our novel summary data technique to test drugs in animal models more appropriate to the human stroke paradigm than have been used in the past In clinical studies we will follow our theme of identifying new targets for therapy using sophisticated PET and MRI imaging techniques, both in patients who are at great risk of stroke recurrence after a minor warning stroke and those with stroke caused by bleeding within the brain. These studies will provide information about predictors of recurrent and worsening stroke which may be modified by new therapies. The final stage in identifying new therapies is the Phase III clinical trial. We will complete one of these in which the most appropriate drug preventing further strokes in a major new stroke subtype will be identified. Toward the end of the program, we will commence phase 3 studies of drugs we have selected as being most likely to protect the brain based on our animal experiments. The main benefit of this unique collaborative research model is to efficiently identify new therapies to reduce the burden of stroke, currently the second most common cause of death globally.Read moreRead less
Role Of Post-traumatic Hypoxia In The Exacerbation Of Cerebral Inflammatory Response Elicited By Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$397,535.00
Summary
Traumatic brain injury is the major cause of death in the young population below the age of 40 years. Approximately 25% of patients that survive head injury remain with permanent neurological disabilities with considerable family, professional and economic costs. Extensive research has shown that not all brain damage occurs at the time of injury, but rather evolves over the hours and days following trauma. Secondary injury may result from various factors including hypoxia (insufficient oxygen) a ....Traumatic brain injury is the major cause of death in the young population below the age of 40 years. Approximately 25% of patients that survive head injury remain with permanent neurological disabilities with considerable family, professional and economic costs. Extensive research has shown that not all brain damage occurs at the time of injury, but rather evolves over the hours and days following trauma. Secondary injury may result from various factors including hypoxia (insufficient oxygen) as a consequence of respiratory distress that occurs in about 50% of patients with severe head trauma. Hypoxia is known to significantly worsen the neurological impairment and potentially lead to death. Brain injury and hypoxia have the ability to separately trigger cerebral inflammation. A dual role has been attributed to inflammation: to promote tissue repair but also add further damage through the release of neurotoxic substances. We hypothesise that hypoxia occurring after traumatic brain injury enhances the inflammatory response in the brain and aggravate tissue damage as well as neurological dysfunction. This hypothesis will be tested on a rat model of brain injury whereby the animals will be exposed to moderate-severe hypoxia immediately after trauma. The production of multiple inflammatory mediators will be quantified in the brain tissue and also in cerebrospinal fluid. The concentration of these mediators will be compared with the levels of cellular injury proteins known to increase following injury to determine whether a correlation exists. In a clinical study on patients, we will measure the same inflammatory mediators and proteins in the cerebrospinal fluid and blood of individuals with severe head injury. The suitability of these factors for potential use as diagnostic-prognostic markers of either hypoxia or injury will be determined.Read moreRead less