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
Therapy For CNS Degeneration In MPS Disorders That Targets Both Glycosaminoglycan And Ganglioside Storage.
Funder
National Health and Medical Research Council
Funding Amount
$368,043.00
Summary
Children with seven of the eleven types of mucopolysaccharidosis (MPS) disorders exhibit a profound, irreversible neurological deterioration that manifests in infancy. This results from the continual buildup of undegraded sugar and fat in brain cells. The goal of this proposal is to prevent the accumulation of lipid alone or both lipid and sugar in the brain in order to alter the progression of neurological disease. Treatment will be assessed in mouse models of MPS.
DEVELOPMENT OF CARDIOVASCULAR CONTROL DURING SLEEP IN HUMAN INFANTS AFTER PRETERM BIRTH
Funder
National Health and Medical Research Council
Funding Amount
$358,537.00
Summary
Infants spend the major part of their life in sleep, and the period between birth and 6 months of age sees dramatic changes in their sleep organisation. Coincidently, there are dramatic developmental changes in the infant's heart and blood pressure control systems, and the ability to compensate for stress such as falls of blood pressure (hypotension) or in the level of oxygen in the blood (hypoxaemia). In infants born preterm, the risks of hypoxaemia, and even death are significantly greater dur ....Infants spend the major part of their life in sleep, and the period between birth and 6 months of age sees dramatic changes in their sleep organisation. Coincidently, there are dramatic developmental changes in the infant's heart and blood pressure control systems, and the ability to compensate for stress such as falls of blood pressure (hypotension) or in the level of oxygen in the blood (hypoxaemia). In infants born preterm, the risks of hypoxaemia, and even death are significantly greater during sleep than during wakefulness, but why this is so is uncertain. This study will examine the ability of infants to respond to stress during sleep. Four groups of infants will be examined: healthy infants born at normal gestation; healthy infants born prematurely (preterm); preterm infants who have experienced mild hypoxaemia soon after birth; and preterm infants who have suffered more severe hypoxaemia because of lung disease. Infants will be studied in a sleep laboratory during day-time sleep, and their ability to control blood pressure will be determined. By contrasting the effectiveness of blood pressure control between the infant groups we aim to determine whether preterm infants have lasting problems as a result of their premature birth, or their exposure to hypoxaemia. By contrasting infants in sleep and wakefulness, we aim to assess whether the risks of poorer blood pressure control are greater in sleep.Read moreRead less
Maternal Gut Microbiome During Pregnancy Influences Offspring Atopy And Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$46,622.00
Summary
Allergic diseases such as food allergy and asthma have increased significantly as our exposure to bacteria has reduced. Many studies have explored exposure to bacteria in early life but few have examined the maternal bacteria we are exposed to while we develop in the womb. New studies indicate that we are exposed to many different components of our mothers gut bacteria and this might change our developing immune system and determine whether or not we get diseases like food allergy and asthma.
The Relationship Between Maternal And Infant Dietary Intake Of Fermentable Fibre, Gut Microbiota, Short Chain Fatty Acids And Allergic Disease And Asthma: A Population-derived Birth Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$871,700.00
Summary
The proposed study will involve the Barwon Infant Study (BIS) cohort of 1074 infants to provide the first systematic investigation of the hypotheses that the epidemic of allergic disease and asthma in many parts of the world relates to the paucity of fermentable fibre in the modern diet, and that the protective effect of fermentable fibre is mediated by changes in the organisms that colonise the gut and the metabolites that they produce.
Modified Peanut Allergen Combined With A Novel Dietary Adjuvant As A Cure For Peanut Allergy: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,130,021.00
Summary
Peanut allergy is common and there is no cure. Current studies of peanut immunotherapy have shown the effects are not generally long lasting with many side effects. We plan to study a novel form of oral peanut immunotherapy using modified peanut and a dietary fibre (modified starch) supplement. We have evidence that modified peanut may work to desensitise patients with less side effects and that the diet supplement protects animals from developing food allergy.
Multi-centre, Multi-disciplinary Study Using A Systems Biology Approach To Investigate Immunomodulation In Children With Acute Wheeze
Funder
National Health and Medical Research Council
Funding Amount
$1,895,107.00
Summary
The concept that immunomodulation using naturally-occurring bacterial agents can treat asthma has reached international prominence. This is backed by strong epidemiologic and clinical trial data. However, detailed knowledge of the immunological mechanisms involved is essential to allow more focused therapeutic agents to be developed. The proposed multi-disciplinary immunomodulation study in 200 children aims to provide this essential information using an advanced systems biology approach.