Molecular And Clinico-pathological Investigation Of Congenital Myopathies
Funder
National Health and Medical Research Council
Funding Amount
$743,290.00
Summary
Congenital myopathies are inherited disorders causing muscle weakness from birth. Some types lead to early death of the affected child, while others are compatible with life to adulthood. Like any disease of childhood, the congenital myopathies cause considerable trauma to the families concerned. Couples at risk of having another affected child frequently wait for prenatal diagnosis to become available for their particular disease before attempting to have further children. However, prenatal dia ....Congenital myopathies are inherited disorders causing muscle weakness from birth. Some types lead to early death of the affected child, while others are compatible with life to adulthood. Like any disease of childhood, the congenital myopathies cause considerable trauma to the families concerned. Couples at risk of having another affected child frequently wait for prenatal diagnosis to become available for their particular disease before attempting to have further children. However, prenatal diagnosis is only possible once the gene causing a disorder and the mutation in an individual family are identified. In the past, the Laboratories collaborating in this project, the Molecular Neurogenetics Laboratory, Australian Neuromuscular Research Institute, Perth, and the Neurogenetics Research Unit, New Children s Hospital, Sydney, have identified disease genes for congenital myopathies. Prenatal diagnosis is now possible for families whose disease-causing mutation is identified. However the genetic cause of many of the congenital myopathies remains unknown. DNA and other samples have been sent to the Laboratories from around the world, making us reference centres for congenital myopathy research. Part one of the project is to study these and Australasian samples, to identify other congenital myopathy genes. This will help families who currently cannot have prenatal diagnosis. Finding the genes also increases understanding of the diseases by clarifying which proteins are involved. In part two of the project we shall study the mutated proteins, to try to unravel how the gene mutations cause the diseases. The third part of the project is to reevaluate the highly variable muscle pathology in congenital myopathies in cases where the disease gene is now known, in order to investigate genotype-phenotype correlations. Understanding the pathologic basis of the congenital myopathies will ultimately allow us to begin to think rationally about possible treatments.Read moreRead less
The Use Of Minimal Residual Disease Detection To Improve Treatment Outcome In Childhood Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$316,650.00
Summary
Leukaemia is the most common childhood cancer, representing approximately 35% of all cases. Despite intensive therapy, the disease frequently recurs in the bone marrow and although children are classified into good and poor prognosis groups at diagnosis based on a number of criteria, relapses nevertheless occur in both groups. Available evidence suggests that early detection of poor treatment response in the otherwise good prognosis group, and the implementation of alternative therapy when the c ....Leukaemia is the most common childhood cancer, representing approximately 35% of all cases. Despite intensive therapy, the disease frequently recurs in the bone marrow and although children are classified into good and poor prognosis groups at diagnosis based on a number of criteria, relapses nevertheless occur in both groups. Available evidence suggests that early detection of poor treatment response in the otherwise good prognosis group, and the implementation of alternative therapy when the cancer burden is at a low level, has a high likelihood of improving patient survival. The failure to respond well to treatment is assessed by a novel molecular genetic technique developed in our laboratory that can detect and quantitate very low levels of residual leukaemia with great sensitivity and specificity. The major goal of this project is to conduct a clinical trial in which this testing procedure is used at an early stage of treatment, and patients who have a bad result on this test, will be given more intensive treatment to see if this improves survival rates. In addition, the project is also directed towards investigating a range of genes known to have a role in drug detoxification. A number of naturally occurring variations exist for these drug metabolising genes and there is evidence suggesting that specific variations or patterns may influence a cancer's response to treatment. We will therefore examine the genetic patterns present in a large cohort of leukaemias and correlate these patterns with response to treatment. It is anticipated that these studies will help define the most appropriate treatment strategies for children with leukaemia. This project therefore has major implications for the therapeutic management of children with leukaemia and has the potential of contributing directly to the improved survival of this most common of childhood cancers.Read moreRead less
A Stable Protein:DNA Complex For Development Of Ultrasensitive Diagnostics In Multiplex Format
Funder
National Health and Medical Research Council
Funding Amount
$521,961.00
Summary
A new technology platform will be developed to carry out diagnostic tests in a multiplex format with increased sensitivity and precision. We recently discovered a very strong interaction between a protein and a particular fragment of DNA. This interaction can be tuned to enable its use for the simultaneous detection of different disease markers in a single assay. This will improve the time and space needed to perform diagnostic tests in laboratories.
The Use Of Minimal Residual Disease Detection To Improve Treatment Outcome In Childhood Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$374,625.00
Summary
Leukaemia is the most common childhood cancer, representing approximately 35% of all cases. Despite intensive therapy, the disease frequently recurs in the bone marrow and although children are classified into good and poor prognosis groups at diagnosis based on a number of criteria, relapses nevertheless occur in both groups. Evidence obtained by ourselves and others, suggests that early detection of poor treatment response in the otherwise good prognosis group, and the implementation of altern ....Leukaemia is the most common childhood cancer, representing approximately 35% of all cases. Despite intensive therapy, the disease frequently recurs in the bone marrow and although children are classified into good and poor prognosis groups at diagnosis based on a number of criteria, relapses nevertheless occur in both groups. Evidence obtained by ourselves and others, suggests that early detection of poor treatment response in the otherwise good prognosis group, and the implementation of alternative therapy when the cancer burden is at a low level, has a high likelihood of improving patient survival. In this regard, we have recently developed a novel molecular genetic technique that can detect and quantitate very low levels of residual leukaemia with great sensitivity and specificity. This technique is ideally suited for use in the routine clinical setting, and as a result of this development, we have now established a clinical trial (ANZCCSG Study VIII) in which patients who have a bad result on this test, will be given more intensive treatment to see if this improves survival rates. A number of research questions will also be addressed in this trial including whether the level of residual leukaemia at the end of therapy is able to predict future relapse that would otherwise not be suspected. It is anticipated that the clinical trial will help define the most appropriate treatment strategies for children with leukaemia. This project, which is at the forefront of such studies worldwide, has major implications for the therapeutic management of children with leukaemia and has the potential of contributing directly to the improved survival of this most common of childhood cancers.Read moreRead less