Targeted Corrective Gene Conversion (TCGC): Application In DMD Mutations And Delivery To Dystrophic (mdx) Muscle
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
The muscular dystrophies are inherited diseases that lead to muscle wastage and severe disabilities. The most severe forms result in the early death of newborns, but a large number are diagnosed in children showing early mild symptoms and progress steadily to severe disabling forms in the juvenile and young adult. Perhaps the most devastating of these dystrophies is Duchenne Muscular Dystrophy (DMD). This condition affects 1 in 3,300 boys, who show symptoms at around 5 years of age until wheelch ....The muscular dystrophies are inherited diseases that lead to muscle wastage and severe disabilities. The most severe forms result in the early death of newborns, but a large number are diagnosed in children showing early mild symptoms and progress steadily to severe disabling forms in the juvenile and young adult. Perhaps the most devastating of these dystrophies is Duchenne Muscular Dystrophy (DMD). This condition affects 1 in 3,300 boys, who show symptoms at around 5 years of age until wheelchair confinement by early teens. DMD boys undergo major clinical and surgical treatments which at present only provide small but significant improvements to their lives. The median age at death for Duchenne boys is 22 years. The cause of DMD has been known for almost 2 decades and is a defect in just a single component of muscle, Dystrophin which is produced by muscle cells. In general, boys with DMD possess Dystrophin which is missing an important part that prevents the breakdown of muscles during activity. As a consequence, all the muscles in DMD boys slowly break down over their lifetime until they die because the muscle which helps in drawing breath (Diaphragm) is no longer capable of helping them to breathe. The muscle component Dystrophin is produced by a gene (the dys gene) and the defect of Dystrophin is caused by a defect in the dys gene. If the dys gene defect was able to be corrected in boys with DMD, their Dystrophin may also be corrected and the breakdown of their muscle prevented. We have been able to correct the dys gene in muscle cells from a mouse with DMD. We wish to improve this technology and allow muscle to be corrected with genetically corrected fibres to form a basis for treatment of human DMD. In this way we hope to significantly improve and lengthen these boys' lives and even lead to a cure for DMD and other genetic muscle diseaseRead moreRead less
A Motion Correction Technique For Accurate PET/CT Brain Imaging In Paediatric And Dementia Patients
Funder
National Health and Medical Research Council
Funding Amount
$190,450.00
Summary
PET-CT imaging is a vital tool in the diagnosis and management of patients with brain disorders including dementia, epilepsy and cancer. However images are often distorted by patient motion, particularly in demented and paediatric patients. The CI has recently developed a motion tracking and correction method to derive images nearly free of motion effects. This aim of this project is to evaluate its impact on image quality in a variety of patients referred for PET- CT brain investigations.
Control Of Refractive Error Through Ionically Driven Fluid Movements
Funder
National Health and Medical Research Council
Funding Amount
$208,600.00
Summary
Myopia affects about half the world's population with recent studies suggesting epidemic proportions among some Asian schoolchildren though we are not seeing this in Australia. Costs associated with detection, monitoring and optical correction of low and high myopia are huge. High myopes (15% with > 6D) also have a greatly increased risk of blindness between the ages of 30 and 50 years due to secondary disorders associated with impaired fluid balance (retinal and choroidal oedema, macula oede ....Myopia affects about half the world's population with recent studies suggesting epidemic proportions among some Asian schoolchildren though we are not seeing this in Australia. Costs associated with detection, monitoring and optical correction of low and high myopia are huge. High myopes (15% with > 6D) also have a greatly increased risk of blindness between the ages of 30 and 50 years due to secondary disorders associated with impaired fluid balance (retinal and choroidal oedema, macula oedema, retinal detachment and glaucoma). Currently there is no accepted pharmaceutical treatment for myopia though our studies in chick have provided the theoretical rationale and experimental data for a potential therapy and patent. This patent is now at the PCT stage and attests that changes in the abundance of the ions of the subretinal space control fluid movements across the retina to choroid and can be modulated therapeutically by diuretics to control fluid flow and hence axial growth and myopia. This application aims to take our current knowledge about fluid control in myopic chick into a mammalian model prior to preclinical trials in monkey. We anticipate it will take 1 year to establish the feasibility of diuretic control of experimentally induced myopic refractive errors in guinea pigs and the best drug and best the dosage range. These studies will contribute to the scientific understanding and bring the proposed pharmaceutical therapy for myopia in adults and children to a point of full commercialization. We believe that the results found in chick will have significance for early and late-onset myopia in humans as it is highly likely that the same mechanisms of ocular growth regulation operate throughout life.Read moreRead less
The Clinical Impact Of Event-based Motion Correction In Paediatric PET-CT Brain Imaging
Funder
National Health and Medical Research Council
Funding Amount
$276,104.00
Summary
Movement of the head during PET-CT brain imaging can prevent accurate diagnosis by blurring and distorting the image. The problem is perhaps most acute in paediatric patients, many of whom must be anaesthetized or sedated to avoid motion. This work will establish whether a recently developed motion correction method can improve the clinical utility of PET-CT brain images in young patients, and reduce the need for sedation and anaesthesia during the PET scan.
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.
Epilepsy is a very common and serious brain disorder. Epilepsy often includes other disabilities, reduction in quality of life and is associated with increased risk of early death. 30% of people with epilepsy are unable to gain control of their seizures with currently available medications. The genetic causes of the large majority of epilepsy cases have not yet been found. This project aims to identify new genetic causes of epilepsy and its related disorders.