Epileptic convulsions are common, disrupt social life and may occasionally cause death. They can occur spontaneously in individuals whose brains appear to be physically normal. Apart from the fact that epilepsy may run in families, the processes leading to spontaneous convulsions are not known. We measure the brain's electrical rhythms (EEG) to find out which rhythms are disturbed in people with epilepsy and whether these rhythms disrupt the brain to cause attacks. In preliminary studies in pati ....Epileptic convulsions are common, disrupt social life and may occasionally cause death. They can occur spontaneously in individuals whose brains appear to be physically normal. Apart from the fact that epilepsy may run in families, the processes leading to spontaneous convulsions are not known. We measure the brain's electrical rhythms (EEG) to find out which rhythms are disturbed in people with epilepsy and whether these rhythms disrupt the brain to cause attacks. In preliminary studies in patients with generalised epilepsy, we have identified abnormally strong rhythms that are almost certainly related to epilepsy causation and our studies are in part aimed at making our findings into a diagnostic test. Our findings may even enable individuals with epilepsy to test themselves for their immediate risk of seizure. Both of these outcomes should enable improved treatment for epilepsy. In addition to benefits in epilepsy, there are potential benefits in the diagnosis of cerebral degenerative disorders if changes in the rhythms also occur in these conditions.Read moreRead less
What Drives Abnormal Cerebral Activity In Secondary Generalised Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$565,809.00
Summary
Secondary Generalised epilepsy (2GE) is a severe, disabling epilepsy syndrome characterised by childhood onset frequent, treatment resistant seizures and developmental delay. Although one of the four major categories of epilepsy, it is poorly understood. This project uses combined EEG (brainwave testing) and MRI to reveal which brain areas are involved in the epileptic activity of 2GE. Advanced analysis techniques will explore which brain regions initiate 2GE epileptic activity.
Health-Related Quality Of Life In Intractable Paediatric Epilepsy: Using A New Measure To Improve Management
Funder
National Health and Medical Research Council
Funding Amount
$252,940.00
Summary
Until recently there was no adequate measure to assess the quality of life of children with epilepsy. Our Australian centre was the first to develop, validate and publish such an instrument; the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). We now aim to collect more data using the QOLCE to gain further understanding of the effects of epilepsy and its treatment on the quality of life of children. We will determine if surgery in children stops seizures and improves quality of life. ....Until recently there was no adequate measure to assess the quality of life of children with epilepsy. Our Australian centre was the first to develop, validate and publish such an instrument; the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). We now aim to collect more data using the QOLCE to gain further understanding of the effects of epilepsy and its treatment on the quality of life of children. We will determine if surgery in children stops seizures and improves quality of life. We also aim to find out if children with different types of epilepsies have unique quality of life issues. Finally, we aim to determine if the quality of a child's life depends on how well they are thinking and learning or how often they are having seizures. We will conduct this study in children with difficult epilepsy recruited from three major children's hospitals (Sydney Children's Hospital, the Children's Hospital, Westmead, Miami Children's Hospital, Florida USA) using a well designed methodology. Each child will have their particular type of epilepsy characterised using video and brain wave analysis. Each parent and older child will receive a quality of life package including the QOLCE to assess life function. In addition, all children will have an assessment of their thinking and learning by a child psychologist. At the completion of this project we will have established whether surgical treatment in children with epilepsy stops seizures and improves quality of life. This will allow clinicians and parents to better understand the effects of surgical treatment in this population. In addition, we will determine if problems in quality of life are associated with specific types of epilepsy. This information can be used to counsel families and tailor interventions and treatments. Finally, we will know whether a child's quality of life is determined by problems with thinking and learning and-or seizures.Read moreRead less
Altered HCN Channel Expression And Function In Acquired Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$279,912.00
Summary
About 100 000 people currently suffer from epilepsy in Australia and of these about one third are poorly controlled with current anti-epileptic drugs. It is therefore important to continue to develop novel modes of treatment for this debilitating disease. This projects investigates an ion channel, known as the HCN channel, that is thought to be involved in making a brain epileptic. We explore how changes in this channel can make a brain more excitable. Also, our group is the first in the world t ....About 100 000 people currently suffer from epilepsy in Australia and of these about one third are poorly controlled with current anti-epileptic drugs. It is therefore important to continue to develop novel modes of treatment for this debilitating disease. This projects investigates an ion channel, known as the HCN channel, that is thought to be involved in making a brain epileptic. We explore how changes in this channel can make a brain more excitable. Also, our group is the first in the world to discover a mutation in this channel that is linked to epilepsy. We will also investigate how this mutation changes the channel properties to make a brain more likely to be epileptic. The HCN channel is an important target for developing anti-epileptic drugs. Understanding how changes in HCN channels make nerve cells and therefore nerve cell networks more excitable will help us develop better strategies for designing anti-epileptic drugs.Read moreRead less
Development Of Dynamin Inhibitors As Novel Therapies For Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$903,376.00
Summary
Epilepsy affects 1% of people, but 30% do not respond to current anti-epileptic drugs (AEDs). Traditional drug discovery has not improved this situation. Our team discovered two exciting new targets for design of better AEDs. One of them blocks seizure in animals. Our aim is to determine how well they work in true animal models of epilepsy. If successful, this will accelerate development of new AEDs with less side-effects, benefiting large sectors of the Australian community.
Do Changes In HCN Channels Function Cause Epilepsy?
Funder
National Health and Medical Research Council
Funding Amount
$386,172.00
Summary
About 100 000 people suffer from epilepsy in Australia with about one third poorly controlled with current anti-epileptic drugs. It is important to continue to develop novel modes of treatment for this debilitating disease. This project investigates an ion channel, known as HCN that is thought to be involved in making a brain epileptic. Understanding how changes in HCN channels make nerve cells and nerve networks more excitable will help us develop better strategies for designing drugs.
Anxiolytic And Anti-epileptogenic Roles Of Brain Protease-activated Receptor (PAR2)
Funder
National Health and Medical Research Council
Funding Amount
$262,073.00
Summary
Epilepsy and anxiety are two of the most common chronic brain conditions world-wide, affecting hundreds of millions people worldwide, and are associated with a considerable burden of disability, impaired quality of life, a range of co-morbidities (eg physical injury, psychiatric disorder) and premature death. People who develop epilepsy have often experienced an initial insult (e.g. head trauma, brain inflammation, febrile convulsions) and then live for months to years before seizures develop. T ....Epilepsy and anxiety are two of the most common chronic brain conditions world-wide, affecting hundreds of millions people worldwide, and are associated with a considerable burden of disability, impaired quality of life, a range of co-morbidities (eg physical injury, psychiatric disorder) and premature death. People who develop epilepsy have often experienced an initial insult (e.g. head trauma, brain inflammation, febrile convulsions) and then live for months to years before seizures develop. This latent period between the initial insult and the onset of recurrent seizures is referred to as epileptogenesis - the transformation of the brain from the non-epileptic to the epileptic state in which a vicious cycle develops where 'seizures beget seizures.' This process cannot currently be prevented once it begins. A similar process has been implicated in the development of chronic anxiety, with an initial early life brain insult or stress and the emergence of the condition later in life. There are no treatments to prevent or cure either disease, only drugs to alleviate the symptoms. We, however, have now discovered that a small protein, called, SLIGRL that activates cell detector molecules called PAR2 which are involved in controlling brain inflammation, inhibits epileptogenesis and anxiety in well-defined rodent models. In the experiments outlined in this grant, we will confirm these very exciting preliminary findings in other models of epileptogenesis and anxiety, as well as determine the underlying mechanisms of the protection. We will also examine if SLIGRL helps prevent a peripheral inflammatory diseases - colitis - by an anti-inflammatory action in the brain similar. The main outcome of our study will be important proof-of-principle data for the development of drugs like SLIGRL for clinical use for the treatment of epilepsy, anxiety and possibly other brain diseases where inflammation plays an important role.Read moreRead less
NPY Suppresses Seizures And Modulates Thalamocortical Activity In Animal Models Of Generalized Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$386,020.00
Summary
Epilepsy is the most common serious chronic neurological disease in the community, affecting up to 3% of the population in a lifetime and 0.5-1% at any one time. Absence epilepsy is one of the most common types of epilepsy, most frequently seen in childhood and teenage years that may persist into adulthood. Anti-epileptic drugs are effective in controlling absence seizures in most patients, however there is an important group (20-40%) of patients in whom the absence seizures remain uncontrolled ....Epilepsy is the most common serious chronic neurological disease in the community, affecting up to 3% of the population in a lifetime and 0.5-1% at any one time. Absence epilepsy is one of the most common types of epilepsy, most frequently seen in childhood and teenage years that may persist into adulthood. Anti-epileptic drugs are effective in controlling absence seizures in most patients, however there is an important group (20-40%) of patients in whom the absence seizures remain uncontrolled with current medications. Recently there has been considerable interest in the role that chemical in the brain, such as neuropeptide Y (NPY), may play in epilepsy. The research proposed will examine the role of NPY in several animal models of absence epilepsy. We have recently shown that NPY suppresses absence seizures in a rat genetic model of generalised epilepsy, and that this appears to be mediated by Y2 receptors. This work will build on these novel findings, and determine the localisation of the effect within the brain, and the underlying mechanism. We will check NPY effects across several models in different species, a genetic rat model with spontaneous seizures, and in mice treated with a chemical to induce seizures. This will determine its broad applicability. We will also determine the effects of removal of NPY or NPY receptors on the effects of NPY on seizure expression. Finally, brain recording techniques will be applied to determine the mechanism and site within the brain underlying the protective actions of NPY. The project has the potential to provide novel insights into the role of NPY in the expression and modulation of absence seizures. NPY related mechanisms might represent targets for the development of a new class of therapeutic agents for the treatment of absence epilepsy. Targets that are identified as being important in the expression of absence seizures may also prove to be relevant in other types of generalised epilepsy syndromes.Read moreRead less
Investigating Genetic Determinants Of Absence Epilepsy In A Polygenic Rat Model
Funder
National Health and Medical Research Council
Funding Amount
$458,481.00
Summary
The underlying genetic causes of idiopathic generalised epilepsies (IGE) are still largely unknown. In an animal model of IGE we have discovered novel genetic abnormalities an ion channel. This proposal will build upon these novel findings to examine the role these abnormalities have in determining the absence epilepsy phenotype and this work has the potential to provide vital information regarding the mechanisms by which this gene contributes to an IGE seizure phenotype.