This project aims to investigate novel ways to treat children with the inherited brain disorder known as MPS IIIA. This condition is currently untreatable and children generally die in their teens. We will use a mouse model of this condition to examine the effectiveness of combining two different treatment approaches, in order to maximise outcomes.
Generation And Characterisation Of An Animal Model For Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$226,650.00
Summary
Age-Related Macular Degeneration (AMD) is the leading cause of irreversible blindness in the aged population in the developed world, and it is one of the least understood retinal diseases. AMD is a slow, progressive and painless condition that affects the macula, the small central part of the retina that allows one to see fine detail clearly. With the ever-increasing human life expectancy, the prevalence of AMD (15-30%) in the age group of over 75 years will significantly increase, causing enorm ....Age-Related Macular Degeneration (AMD) is the leading cause of irreversible blindness in the aged population in the developed world, and it is one of the least understood retinal diseases. AMD is a slow, progressive and painless condition that affects the macula, the small central part of the retina that allows one to see fine detail clearly. With the ever-increasing human life expectancy, the prevalence of AMD (15-30%) in the age group of over 75 years will significantly increase, causing enormous social and financial problems for the community. In spite of the significance of this problem, the exact cause of AMD is not yet known, and there is no permanent effective treatment or cure for the condition. One of the major obstacles hindering any advances towards the development of intervention strategies or therapies is the lack of an appropriate animal model. Currently, the animal models that are available for ocular diseases do not fit the human AMD situation. This project aims to characterize the first animal model for retinal degeneration caused by abnormal functioning of the retinal pigment epithelial cells (RPE). The main role of RPE cells is the phagocytosis and digestion of the continuously growing and shed light receptor segments in the eye. Their normal functioning therefore is vital to maintaining good vision. The availability of such an animal model will allow us to learn more about the changes that might occur in the eye leading to the development of AMD and to design strategies to prevent or delay progression of the condition.Read moreRead less
Cisterna Magna Delivery Of Therapeutic Lysosomal Enzyme To Correct CNS Pathology In Lysosomal Storage Disorders
Funder
National Health and Medical Research Council
Funding Amount
$760,282.00
Summary
Lysosomal storage disorders (LSD) are inherited diseases that affect about 1 in 7700 Australian children; all share common physical symptoms include heart and breathing difficulties, stiff joints, skeletal deformities, enlarged head, and a characteristic facial appearance. Two-thirds of patients will also develop brain disease. The lysosome is a component of each cell in the human body; its role it is to break down and remove waste from the cell. This involves a series of proteins (enzymes) that ....Lysosomal storage disorders (LSD) are inherited diseases that affect about 1 in 7700 Australian children; all share common physical symptoms include heart and breathing difficulties, stiff joints, skeletal deformities, enlarged head, and a characteristic facial appearance. Two-thirds of patients will also develop brain disease. The lysosome is a component of each cell in the human body; its role it is to break down and remove waste from the cell. This involves a series of proteins (enzymes) that act in sequence. A LSD arises when the lysosome lacks the activity of one protein in this chain. The loss of protein activity impairs the waste removal process. Waste begins to 'store', clogging the cell and interfering with its usual functions. This gives rise to devastating symptoms that worsen over time as storage increases. Brain disease in LSD has profound effects on the child: mental capacity declines, they become hyperactive and aggressive and progressively lose learned skills (e.g. walking, talking) and ability to control bodily functions. Artifically made protein is being successfully used to treat some LSD via intravenous injection. However, it is not able to access the brain because of a protective barrier that surrounds it. This project tests a method to deliver protein to the brain to reduce and stop waste build-up. It involves the injection of artificially made protein into the fluid surrounding the brain and spinal cord using techniques being used to treat other diseases. This method is likely to be the quickest way in which we can treat both the body AND the brain of an affected child. We have diagnosed animal models who were born with a LSD with brain disease, called MPS IIIA. Their symptoms are similar to that seen in humans over the course of the disease, making them ideal for study in this project. Success in this project will allow us to advance this treatment to human trials.Read moreRead less
Development Of A Safe And Effective Treatment For Neuropathology In MPS IIIA.
Funder
National Health and Medical Research Council
Funding Amount
$665,320.00
Summary
MPS IIIA is an inherited disorder that results in progressive brain disease in affected children. The disorder cannot be treated at present because it has not been possible to find an effective way to deliver treatment to the brain. This project seeks to evaluate a method to overcome this problem. Findings in this project can be applied to other, similar disorders that affect the brain.
I am an immunochemist-cell biologist investigating the involvement endosomes and lysosomes in different disease states. A primary focus has been on the group of diseases called lysosomal storage disorders where early diagnostic and effective treatment strategies have been and continue to be developed. Due to the multi-functionality of endosomes and lysosomes, these critical organelles are also involved in the pathology caused by other major diseases like bacterial infection and cancer, and this ....I am an immunochemist-cell biologist investigating the involvement endosomes and lysosomes in different disease states. A primary focus has been on the group of diseases called lysosomal storage disorders where early diagnostic and effective treatment strategies have been and continue to be developed. Due to the multi-functionality of endosomes and lysosomes, these critical organelles are also involved in the pathology caused by other major diseases like bacterial infection and cancer, and this is being actively investigated.Read moreRead less
Treatment Of Lysosomal Storage Disorder Patients By Drug-enhanced Premature Stop Codon Read-through
Funder
National Health and Medical Research Council
Funding Amount
$431,764.00
Summary
Lysosomal storage disorders are a devastating set of genetic diseases with very severe clinical symptoms. In this project, we will investigate a new treatment strategy that is non-invasive and that will be applicable for a wide range of lysosomal storage disorder patients. The therapy will over-ride the molecular genetic lesion and will be preferentially targeted for patients who are at the severe end of the clinical spectrum, where treatment options are currently limited.
Evaluation And Comparison Of Lentiviral And AAV Vector Mediated Gene Therapy For The Mucopolysaccharidoses
Funder
National Health and Medical Research Council
Funding Amount
$521,320.00
Summary
The mucopolysaccharidoses are a group of inherited diseases that have profound consequences for affected individuals. They have pleiotropic effects and usually result in premature death. Although intravenous enzyme replacement therapy has been developed for a number of these disorders, this approach to therapy is invasive, very expensive, of limited efficacy, and is completely ineffective in treating brain pathology. The principal reason for this is the protected nature of the brain which preven ....The mucopolysaccharidoses are a group of inherited diseases that have profound consequences for affected individuals. They have pleiotropic effects and usually result in premature death. Although intravenous enzyme replacement therapy has been developed for a number of these disorders, this approach to therapy is invasive, very expensive, of limited efficacy, and is completely ineffective in treating brain pathology. The principal reason for this is the protected nature of the brain which prevents enzymes that are administered intravenously from entering. Therefore, alternative therapies must be considered in order to provide more effective therapy for the mucopolysaccharidoses, especially those that have significant brain pathology. Gene therapy is one such alternative therapy but this still faces the problem of introducing the therapeutic agent (in this case the gene encoding the requisite enzyme) into the brain. This project aims to provide a comparitive evaluation of two gene therapy vectors for their efficacy in treating all aspects of the pathology found in the mucopolysaccharidoses. Both vectors have the properties of being able to efficiently deliver genes to different cell types and result in the stable genetic modification of the target cell, making them ideal for long-term treatment. However, for effective gene therapy, significant and widely distributed gene delivery to the brain, as well as to other tissues, will be required. This project aims to compare the efficacy of these vectors in two different animal models of the mucopolysaccharidoses that exhibit a wide range of the clinical problems associated with these diseases, importantly including brain pathology.Read moreRead less
Is The Eye A Window To The Brain In Sanfilippo Syndrome?
Funder
National Health and Medical Research Council
Funding Amount
$852,967.00
Summary
Study of the retina and optic nerve permits evaluation of central nervous system – these structures contain both neurons and glia and are outgrowths of the developing brain. Therefore, eye examination may allow us to study the brain and monitor brain disease and the effect of therapy. This project will determine whether brain disease in a childhood-onset disorder (Sanfilippo syndrome) and treatment of it, can be monitored in this way.