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
Neonatal Cranial Ultrasound: Safety, Knowledge And Practice Of Prolonged Or Repeated Exposure To Acoustic Waves
Funder
National Health and Medical Research Council
Funding Amount
$255,055.00
Summary
Ultrasound is routinely used for diagnosis of brain lesions amongst newborns. Animal studies have shown that ultrasound can sometimes be harmful to the brain. We currently have very little information on the characteristics of neonatal cranial scans. This project will investigate current knowledge of safety and training via a nationwide survey, analyse the elements of 'typical' scans and measure brain surface heating after ultrasound amongst neonates.
Centre For Research Excellence In Speech And Language Neurobiology (CRE-SLANG)
Funder
National Health and Medical Research Council
Funding Amount
$2,491,340.00
Summary
Half a million Australian children have a speech/language disorder, tripling their changes of poor academic outcomes, limited employment options and social isolation. Current speech therapy is limited, focusing on symptoms and ignoring evidence on underlying aetiologies. By identifying and translating findings on new genes and brain pathways leading to speech and language disorders, we will transform detection, diagnosis, prognosis and genetic counselling of affected children and their families.
Understanding Typical And Atypical Development Of The Infant Brain
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
This project will apply advanced magnetic resonance imaging (MRI) techniques to understand how brain abnormalities in preterm infants relate to their functional impairments. It aims to: develop new software to easily and accurately measure infant brain structures and tissues; understand the neurobiological basis for adverse outcomes, enabling diagnosis of high risk preterm infants; and identify MRI biomarkers to assess interventions designed to give Australian babies a healthier start to life.
Understanding White Matter Injury In Term-born Children With Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$193,863.00
Summary
The type of brain injury in cerebral palsy varies. In some children the brain develops abnormally in early pregnancy; others have a stroke or suffer from lack of oxygen around the time of birth. Little is known about the group of children born at term who have damage to the brain’s white matter, a pattern more typical of premature birth. This project will explore brain imaging, potential risk factors, and clinical outcomes for these children to identify possible causes and prevention pathways.
Improving Our Understanding Of Causal Pathways To Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The type of brain injury in in children with cerebral palsy varies. In some children the brain developed abnormally in early pregnancy; others had a stroke or suffered from lack of oxygen around the time of birth. In many cases the exact cause remains unclear. This project will explore brain imaging, potential risk factors, and clinical outcomes for children with cerebral palsy to identify possible causes and prevention pathways.
The Burden Of Late Preterm Birth On Brain Development And 2 Year Outcomes – A Prospective, Longitudinal Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$838,690.00
Summary
80% of preterm babies are born from 32-36 weeks’ gestation, and are late preterm (LPT). LPT children have more learning problems, but why this occurs is unknown. This study aims to understand the effect of LPT birth on brain development. We will do brain scans at term and assess development at 2 years of age of 200 LPT and 200 full-term children. We expect LPT babies will have subtle alterations in brain development compared with term controls which will be associated with delayed development.
Metabolic Complications Of Obstructive Sleep Apnea During Early Development
Funder
National Health and Medical Research Council
Funding Amount
$320,375.00
Summary
Adults with OSA are known to have increased risk for heart disease. We will study children with OSA, and an animal model of the disease during early development, to help clarify how this disease of adulthood actually has its origins in childhood. We have already shown that obese children with obstructive sleep apnea (OSA) are more prone to diabetes (metabolic problems) than those without OSA. More recently, we found that this is also true for children who are not overweight. This early diabetes ....Adults with OSA are known to have increased risk for heart disease. We will study children with OSA, and an animal model of the disease during early development, to help clarify how this disease of adulthood actually has its origins in childhood. We have already shown that obese children with obstructive sleep apnea (OSA) are more prone to diabetes (metabolic problems) than those without OSA. More recently, we found that this is also true for children who are not overweight. This early diabetes is known to be to show a future risk for heart disease. This study will examine why OSA in children is linked to metabolic problems. First, we will continue our study in children who are not overweight. We need to study more children to be sure that OSA is truly linked to metabolic problems - whether or not a child is overweight, because this means that children with OSA are at risk for metabolic and future cardiac problems, whether they are overweight or not. Since weight does not usually change after treatment of OSA, we will also study children again, after they have been treated for OSA. We expect to show that treatment of OSA resolves the metabolic problems. Since hypoxia (low oxygen) occurs in OSA we believe that this is the fundamental cause of the metabolic problems. To test whether this is true, we will look for metabolic problems in piglets exposed to similar, low levels of oxygen as those seen in children with OSA, comparing them to piglets that have not been so exposed. We believe that the tendency to develop OSA and diabetes is inherited. To test this, we will study the genes of a very large family whose members have OSA and-or diabetes, and try to find which genes are associated with OSA and with diabetes. This will help determine if the two genes are linked in some way.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.
Executive Dysfunction And Brain Development In Very Preterm 13-year-olds - A Longitudinal MRI Study.
Funder
National Health and Medical Research Council
Funding Amount
$738,656.00
Summary
An area of concern for very preterm children is executive function (i.e. skills used for problem solving), which is related to educational problems, behavioural issues and social difficulties. In very preterm children this study will 1) determine if executive function problems remain stable, worsen, or improve with age; 2) look for markers for these problems from infant brain scans; and 3) examine how executive function difficulties are related to brain re-organisation.