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
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.
Family And Environment In The Development Of Obesity And Precursors Of Diabetes And Heart Disease In Adolescence
Funder
National Health and Medical Research Council
Funding Amount
$284,770.00
Summary
Obesity is a serious public health problem in Australia. The rate of obesity appears to be rising. Currently 19-23% of children and adolescents are overweight or obese. Adolescence is a critical period for the development of obesity in both males and females. It is a time when new dietary habits, likely to promote fatness, are adopted and physical activity declines. Understanding the factors that drive these behaviours is essential for effective prevention of obesity and related diseases. In 199 ....Obesity is a serious public health problem in Australia. The rate of obesity appears to be rising. Currently 19-23% of children and adolescents are overweight or obese. Adolescence is a critical period for the development of obesity in both males and females. It is a time when new dietary habits, likely to promote fatness, are adopted and physical activity declines. Understanding the factors that drive these behaviours is essential for effective prevention of obesity and related diseases. In 1996-7, our research group studied a group of over 400 children who were aged 7-8 years, were living in western Sydney and were born at Nepean Hospital. In our new study, we plan to re-study this group of children, now in early adolescence. This will allow us to assess the family and environmental factors influencing physical activity and eating behaviour at the beginning of adolescence. The aims of our study are to: Measure changes during early adolescence in eating and physical activity behaviours that are likely to increase obesity risk Measure anthropometric and biochemical markers for future risk of type 2 diabetes and cardiovascular disease in both adolescents and their parents Identify factors in the family environment that influence changes in food intake and physical activity in early adolescence The study will be done in two phases, 18 months apart. The measurements will be done in the study centre at Nepean Hospital in western Sydney. We will measure the height, weight and skinfold thickness of the adolescents and, if possible, their parents. We will also ask the young people and their parents to complete questionnaires about the family food and activity environment and their level of physical activity and food intake. In addition, the adolescents will wear a light-weight activity monitor for 3 days ( to measure the level of activity), blood pressure will be measured and cholesterol and blood sugar levels checked.Read moreRead less
RCT Of The Intragastric Balloon And Lifestyle Intervention Versus Lifestyle Intervention Alone In Obese Adolescents
Funder
National Health and Medical Research Council
Funding Amount
$598,976.00
Summary
For the first time in adolescents, Perth researchers will trial placement of a fluid-filled silicone balloon in the stomach. It will be used in conjunction with a lifestyle intervention, and so is expected to increase weight loss. The balloons are safe, effective at adult weight loss and an alternative to invasive surgery. Adolscent obesity rates are rising and treatment options are limited. The non-surgical balloon may be the alternative for adolescents who would previously had to have surgery.
Understanding The Mechanisms Of Bleeding And Clotting Complications For Children On Extracorporeal Circuits.
Funder
National Health and Medical Research Council
Funding Amount
$1,113,385.00
Summary
Extracorporeal Membrane Oxygenation (ECMO) is advanced life support, which can save critically ill children. Significant bleeding occurs in 39%; clotting in 31% of children on ECMO; stroke in 12%. The biggest barrier to reducing these complications is the lack of understanding of how the bleeding/clotting system works in ECMO. This unique proposal uses the largest paediatric ECMO population in Australia and a multidisplinary expert team to develop a mechanistic understanding of these issues.