Long Term Outcomes Of Infant Lung Function In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$509,456.00
Summary
We have shown that babies with cystic fibrosis (CF) who are apparently well can still have lung problems. As lung disease is the major cause of death in CF we need ways to monitor the condition in babies, identify those at greatest risk of lung changes and predict which children should receive newer treatments. We have developed a unique program for the measurement of lung function in babies. We now aim to find out the long term consequences of lung function changes detected in infants with CF.
Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms c ....Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms common to more than one MPS type include mental deterioration, blindness, abdominal organ enlargement and bone growth problems leading to short stature and bone loss. My laboratory has had a long-term interest in developing treatment for MPS and our research led to the clinical implementation of enzyme replacement therapy (ERT) for MPS VI in 2005. While providing the first effective, multi-tissue treatment for MPS, our research showed that several tissues were not responsive to ERT. These are the brain, cartilage and cornea, thus children on ERT regimens will still suffer from mental retardation, arthritis and blindness. With the goal of treating these particular tissues we have developed a new approach to MPS therapy called substrate deprivation therapy (SDT). Instead of adding back the missing enzyme, SDT acts by decreasing gag production which in turn reduces the level of accumulated gag in cells. SDT results in the correction of MPS cells in culture and reduces several key clinical symptoms in the mouse model of MPS IIIA. In this proposal we will extend our research to evaluate the effect of SDT on brain and bone-joint pathology. Evaluation of efficacy will take place in the MPS VII mouse which exhibits both brain and bone disease and in a new model of MPS IVA developed specifically for this study which exhibits a joint pathology unique amongst the MPS disorders.Read moreRead less
I am a perinatal paediatrician undertaking clinically-focussed research on brain development, brain disorders, brain therapies, neurodevelopmental outcomes and the development, application and evaluation of new technology to clinical problems.
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 Long-term Quality Of Life For Preterm Children
Funder
National Health and Medical Research Council
Funding Amount
$638,517.00
Summary
My vision is to improve the long-term quality of life of preterm children (<37 weeks’ gestation), with a specific focus on those born very preterm (VP; <32 weeks’ gestation). To achieve this goal my research has two broad and related aims: 1) Determine the neurological and socio-environmental mechanisms leading to impairments in preterm children; and 2) Develop and assess the efficacy of perinatal and early intervention programs for preterm children.
Neurobehaviour Between Birth And 40 Weeks In Infants Born
Funder
National Health and Medical Research Council
Funding Amount
$832,215.00
Summary
Very preterm infants (born at <30 weeks’ gestation) are at risk of long term developmental problems with 50% having cognitive, motor or behavioural problems. This study will examine, for the first time, neurobehavioral development of very preterm infants from birth so that we can describe neurobehaviour for a given gestation from birth to term equivalent age, and explore how it relates to brain growth or injury and to neurodevelopmental outcome at two years’ corrected age.
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
Australasian Cerebral Palsy Clinical Trials Network (AusCP-CTN): Optimising Interventions And Effective Services For Children With Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$2,499,287.00
Summary
Cerebral Palsy (CP) is common and disability can be progressive so the heathcare burden is immense (0.14% GDP). Our Clinical trials network will improve early detection and develop new interventions to improve physical, cognitive and health outcomes for children with CP and their families. Recruitment from the national CP Register will address clinically important questions and test implementation of effective treatments. New Clinical Practice Guidelines will ensure translation internationally.