Modern Chemical Exposures In Utero And In Infancy, And Their Impact Upon Early Neurodevelopmental Outcomes In The Barwon Infant Study, An Unselected Birth Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$138,353.00
Summary
I am a paediatric doctor interested in the effects of modern industrial chemicals on children’s development. Even in the womb babies are exposed to industrial chemicals and we know some, like lead, are harmful to developing brains. I am interested in other chemicals that are now suspected to affect development, including the polybrominated diphenyl esters (PBDEs), and I intend to investigate this as part of the Barwon Infant Study, which follows 1250 children from before birth to 3 years.
Being Born Small Is Not Good For The Heart:early Detection Of Cardiovascular Risk
Funder
National Health and Medical Research Council
Funding Amount
$486,757.00
Summary
Intra uterine growth restriction(IUGR) is linked to adult onset of cardiovascular disease. However, little is known about the mechanism(s) which underlie this link or which babies are most at risk. This study aims to assess cardiovascular function in infants and children who were growth restricted. Early identification of cardiovascular dysfunction may aid in new opportunities for monitoring and therapeutic targets to ultimately reduce later onset of cardiovascular morbidity in this population.
DETERMINING THE MECHANISMS LEADING TO LONG-TERM IMPAIRMENT IN VERY PRETERM CHILDREN: THE VIBeS LONGITUDINAL STUDY.
Funder
National Health and Medical Research Council
Funding Amount
$1,061,733.00
Summary
Approximately 50% of children born very preterm will develop significant problems. The objective of this project is to determine the mechanisms leading to these problems. We will do this by assessing at school-age a unique and valuable cohort of very preterm infants (VIBeS cohort) who had state-of-the-art brain scans shortly after birth and neurobehaviour assessments across early childhood. This school-age follow-up will involve repeat brain scans and detailed neuropsychological assessments.
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
Neurodevelopmental Outcomes After Novel Interventions In Newborn Infants
Funder
National Health and Medical Research Council
Funding Amount
$188,226.00
Summary
Children who were sick in the newborn period or born preterm are at increased risk of abnormal development, particularly problems with their ability to walk, think and learn. This research will assess how new treatments affect sick newborns’ later development. For example, giving preterm babies healthy germs, or probiotics, decreases a serious bowel infection, called necrotising enterocolitis or NEC. This research will find out if they also help preterm brain development when the children are 2 ....Children who were sick in the newborn period or born preterm are at increased risk of abnormal development, particularly problems with their ability to walk, think and learn. This research will assess how new treatments affect sick newborns’ later development. For example, giving preterm babies healthy germs, or probiotics, decreases a serious bowel infection, called necrotising enterocolitis or NEC. This research will find out if they also help preterm brain development when the children are 2 years old.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.
The Cause Of Undescended Testis And Inguinal Hernia
Funder
National Health and Medical Research Council
Funding Amount
$743,848.00
Summary
This study aims to define in both animal models and children how the testis descends from the abdomen to scrotum, and how undescended testis and inguinal hernia are likely to be caused by defects in the same, very indirect signalling pathway. The results will demonstrate where to look for genetic causes and proof of principle for possible future medical treatments for the 3 commonest major operations in children for congenital and acquired undescended testis and inguinal hernia.
Factor V Leiden Mutation: A Contributory Factor For Cerebral Palsy?
Funder
National Health and Medical Research Council
Funding Amount
$72,595.00
Summary
Cerebral palsy is the commonest physical disability in childhood. It has a major impact on individuals and families. In a significant proportion of cases, the cause is unknown so further research is essential to define the reasons for this condition, and thereby develop preventative strategies. Two mutations have been identified that predispose carriers to develop blood clots (called thrombosis). These mutations are the Factor V Leiden mutation and the coagulation gene for prothrombin (also know ....Cerebral palsy is the commonest physical disability in childhood. It has a major impact on individuals and families. In a significant proportion of cases, the cause is unknown so further research is essential to define the reasons for this condition, and thereby develop preventative strategies. Two mutations have been identified that predispose carriers to develop blood clots (called thrombosis). These mutations are the Factor V Leiden mutation and the coagulation gene for prothrombin (also known as the G20210A mutation). If blood clots form in, or travel to the brain (embolism), they can obstruct the blood supply causing damage that may result in cerebral palsy in young children. Our research will investigate both mothers of children with cerebral palsy, and the children themselves. The study of the mothers will determine whether those that are carriers of these mutations are at an increased risk of having children with cerebral palsy. Factors that may precipitate the development of blood clots, such as smoking during pregnancy, will be investigated. The children with cerebral palsy will be studied to determine whether they carry the mutations, and if so, whether they have brain scan evidence of previous blood clots. Children will be tested for the mutation using the blood spot taken routinely early in life. These blood spots are stored on cards (Guthrie cards) and are available for research following parental consent. The mothers will be tested for the mutation by using a saliva sample and will also be interviewed to obtain details of their pregnancies. As a result of this project, useful information will be provided for families and health care providers. It will be established whether these mutations play a role in the genesis of cerebral palsy. In addition, data about possible factors which may increase the risk in carrier mothers, such as smoking, will be provided.Read moreRead less