Motor problems, ranging from clumsiness to cerebral palsy, are one of the most common adverse outcomes in children born early. This study will investigate the motor development of children born <30 weeks’ gestation compared with peers born at term from birth to 5 years. We will determine whether early clinical evaluations or neuroimaging in the newborn period can predict later motor impairment at 5 years to be able to identify those who will benefit most from early intervention.
The aim of this proposal is to evaluate a novel therapy option for children with a genetic disorder called mucopolysaccharidosis (MPS). MPS arise from the build up of complex carbohydrates in cells within the body due to the deficiency of an enzyme required for their degradation. By decreasing the synthesis of carbohydrate we can manipulate the level of stored carbohydrate and alleviate the pathology associated with MPS. The novel therapy is based on a chemical modification of glucose that inhib ....The aim of this proposal is to evaluate a novel therapy option for children with a genetic disorder called mucopolysaccharidosis (MPS). MPS arise from the build up of complex carbohydrates in cells within the body due to the deficiency of an enzyme required for their degradation. By decreasing the synthesis of carbohydrate we can manipulate the level of stored carbohydrate and alleviate the pathology associated with MPS. The novel therapy is based on a chemical modification of glucose that inhibits carbohydrate synthesis and is termed substrate deprivation therapy.Read moreRead less
Impact Of A Sleep Intervention In ADHD: Translational Randomised Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,020,595.00
Summary
Up to 50% of children with ADHD experience sleep problems which worsen their ADHD symptoms, behaviour, quality of life and day to day functioning. In a previous trial, we showed that treating sleep problems in children with ADHD improves these outcomes. We now want to know if these benefits can be replicated when general paediatrcians and psychologists deliver the same sleep intervention in community settings.
Frontal-striatal-parietal Activation In Children With ADHD, Combined Type: A Functional Magnetic Resonance Imaging Study
Funder
National Health and Medical Research Council
Funding Amount
$91,750.00
Summary
Attention Deficit Hyperactivity Disorder, combined type (ADHD-CT) is a common neuropsychiatric disorder that has serious consequences for affected children's educational and social development and success in later life. Despite a large investment in research investigating aetiology and therapeutic strategies that arise from these aetiological investigations, ADHD-CT remains poorly understood and it is often viewed with therapeutic pessimism. Understanding the neurobiological basis of ADHD-CT is ....Attention Deficit Hyperactivity Disorder, combined type (ADHD-CT) is a common neuropsychiatric disorder that has serious consequences for affected children's educational and social development and success in later life. Despite a large investment in research investigating aetiology and therapeutic strategies that arise from these aetiological investigations, ADHD-CT remains poorly understood and it is often viewed with therapeutic pessimism. Understanding the neurobiological basis of ADHD-CT is of tremendous importance for the development of more specific and targeted medication and-or psychological treatments and, ultimately, to obtain the best clinical outcome for individual children with ADHD-CT. We have previously examined the function of frontal-striatal-parietal brain networks in adolescent boys with ADHD-CT, showing dysfunction of brain systems important for the control of visuospatial attention. In this project, we aim to examine whether these changes in frontal-striatal-parietal brain function also occur in pre-pubertal 8-12 year-old boys with ADHD-CT. This is important for two major reasons: Firstly, adolescents and young adults examined in previous brain imaging studies of ADHD-CT, including our own, are not truly representative of the core of the disorder, as ADHD-CT has its peak prevalence from 8 to 12 years of age. Secondly, by now comparing pre-pubertal ADHD-CT and healthy control children we can determine whether the changes in brain function we have previously identified represent developmental stage independent brain dysfunction that is characteristic of ADHD-CT.Read moreRead less
Skeletal disease is a major problem for children with mucopolysaccharidoses (MPS). Patients suffer from early onset osteoporosis and osteoarthritis, severely affecting their quality of life. We will evaluate a lentiviral gene therapy vector developed in-house for its capacity to transduce bone, cartilage, synovial and ligament cells in a mouse model of MPS VI. Our goal is to generate high level, sustained expression of the deficient MPS enzyme and alter the course of skeletal disease in MPS.
The Effect Of Very Premature Birth On Brain Development
Funder
National Health and Medical Research Council
Funding Amount
$517,975.00
Summary
The neurological outcome of the premature infant is of major importance. Approximately 2,600 premature infants weighing less than 1500 grams are born annually in Australasia. Of the approximate 2,400 survivors between 5-15% will have a more major cerebral palsy, i.e. around 200 children per annum. A greater proportion of 25-50%, i.e., upto 1200 children will have a developmental disability that will adversely affect their school perfomance requiring special assistance or repeating grades. With a ....The neurological outcome of the premature infant is of major importance. Approximately 2,600 premature infants weighing less than 1500 grams are born annually in Australasia. Of the approximate 2,400 survivors between 5-15% will have a more major cerebral palsy, i.e. around 200 children per annum. A greater proportion of 25-50%, i.e., upto 1200 children will have a developmental disability that will adversely affect their school perfomance requiring special assistance or repeating grades. With an increasing number of very prematurely born infants surviving, the absolute number of affected children will continue to rise. Prevention of these disabilities will require an understanding of the cause. The educational and social implications of these high rates of neuro-developmental disability are enormous and the focus of wide international concern. Magnetic Resonance Imaging : It is a major challenge for neonatologists to be able to understand the impact of their therapies and managements on the developing brain. A window into the newborn brain can be seen utilising advanced magnetic resonance imaging techniques in-vivo to investigate these key issues: 1. What is the nature of brain injury in the prematurely born infant? 2. What are the risk factors for brain injury in the prematurely born infant - and are they able to be altered to reduce this risk - e.g. blood pressure management, steroid therapy 3. Is the brain of a prematurely born infant different from that of a full term born infant at TERM equivalent - if so, how is it different? 4. Are there certain postnatal therapies that relate to any alteration in brain structure and chemistry - e.g. postnatal nutrition, modes of ventilation, pharmacological therapies? 5. How does the brain structure relate to function on long term neuro-developmental follow up of our infants at 2 years?Read moreRead less
Improving The Outcome Of Premature Infants- A Randomised Trial Of Preventive Care At Home
Funder
National Health and Medical Research Council
Funding Amount
$633,375.00
Summary
The high rate of adverse neurodevelopmental outcomes of very premature infants is of major concern. In Australia there are approximately 2600 very low birthweight (VLBW, birthweight <1500 g) or very premature (<30 weeks' gestational age) survivors per annum. A large proportion of these infants (40%-50%) will later develop motor incoordination, cognitive impairment, attention deficits or behavioural problems (up to 1300 new cases per year). There is little research to test the efficacy of e ....The high rate of adverse neurodevelopmental outcomes of very premature infants is of major concern. In Australia there are approximately 2600 very low birthweight (VLBW, birthweight <1500 g) or very premature (<30 weeks' gestational age) survivors per annum. A large proportion of these infants (40%-50%) will later develop motor incoordination, cognitive impairment, attention deficits or behavioural problems (up to 1300 new cases per year). There is little research to test the efficacy of early preventive care programs geared to changing the infant's environment (physical management, behavioural regulation, maternal factors). In the proposed study we aim to use a low cost preventive care program at home conducted by physiotherapists and psychologists that has been shown to have utility and efficacy in pilot work, with follow up until 2 years of age. In subsequent studies we would aim to follow this cohort to school age, to determine if there are any lasting benefits of early intervention accompanied by measures of brain growth and structural development using advanced imaging techniques. Any new health care program should result not only in improvements in health, but should be affordable to implement so an economic evaluation will also be undertaken. This study will also utilise novel and advanced MRI brain imaging techniques to understand the complex interaction between brain injury and altered brain development in these infants with the risk and the repsonse to this program of care. In this way the changes in brain connectivity, structure and biochemistry can be formally defined to undertsnad the pathway of any potential benefit from this program.Read moreRead less
The Relationship Between Cognition And Interictal Discharges: Language Organization And Spike Localisation In BECTS
Funder
National Health and Medical Research Council
Funding Amount
$216,500.00
Summary
Benign epilepsy with centro-temporal spikes (BECTS, rolandic epilepsy) is a common cause of seizures in primary school children. Despite this it is poorly understood. Although seizures are infrequent, brainwave recordings (electroencephalography, EEG) reveal striking abnormalities present much of the time. Large, sharply contoured brain waves (spikes) are seen frequently, increasing during sleep. The pattern of the spikes, and the characteristic nature of seizures have suggested the epilepsy ari ....Benign epilepsy with centro-temporal spikes (BECTS, rolandic epilepsy) is a common cause of seizures in primary school children. Despite this it is poorly understood. Although seizures are infrequent, brainwave recordings (electroencephalography, EEG) reveal striking abnormalities present much of the time. Large, sharply contoured brain waves (spikes) are seen frequently, increasing during sleep. The pattern of the spikes, and the characteristic nature of seizures have suggested the epilepsy arises near the face area of the motor cortex, but this remains unproven. Functional magnetic resonance imaging (fMRI) is a safe and non-invasive way of imaging cerebral function, to reveal the brain at work . The technology is contributing to major advances in understanding of basic human functions such as language. Recent developments at the Brain Research Institute in Melbourne mean it is now possible to record EEG during fMRI. This has permitted visualisation of spike activity in the brain. The BRI is the only centre in Australia, and one of only a handful in the world that is able to perform such studies. One purpose of this study is reveal the location of spikes in BECTS. Recent studies have revealed subtle language and learning difficulties in BECTS children. Our preliminary EEG-fMRI studies have suggested spikes arise from brain regions adjacent to important language areas. It is possible that the frequent spikes of BECTS are interfering with adjacent cognitive processes. In addition to spike mapping, we will perform functional imaging of language to look for interactions between spike and language areas, and compare with patterns of language activation seen in normal children. The demonstration of spike related affects on cognition may lead to a reassessment of current epilepsy management strategies, which focus predominately on seizure control. This study, with researchers in Cairns and Melbourne, shares the benefits of world class research with regional Australia.Read moreRead less