Customized IPS Cell Therapy For Recessive Monogenic Retinal Degenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$350,714.00
Summary
The focus of this study is to develop a personalised treatment for certain types of retinal degenerative disease (RDD). Stem cells will be generated from the skin cells obtained from an individual with RDD. Gene therapy will then be applied to correct the underlying disease-causing mutation in the patient cells. The repaired cells will be used to generate retinal cells, which will subsequently be tested in naturally occurring RDD rodent models to determine if they have any beneficial effects.
Cell-targeted Gene Delivery Into Human Haematopoietic Stem Cells For The Treatment Of Thalassaemia
Funder
National Health and Medical Research Council
Funding Amount
$171,208.00
Summary
Thalassaemia is the most common inherited single gene disorder affecting haemoglobin synthesis in red blood cells. It mainly affects people of Mediterranean, Middle Eastern, African, South East Asian, Chinese, and Indian origin. However, large numbers of thalassaemia patients are found nowadays in Australia and other developed countries, due to large population movements in the twentieth century. Approximately 300,000 severely affected children are born each year with thalassaemia and various ot ....Thalassaemia is the most common inherited single gene disorder affecting haemoglobin synthesis in red blood cells. It mainly affects people of Mediterranean, Middle Eastern, African, South East Asian, Chinese, and Indian origin. However, large numbers of thalassaemia patients are found nowadays in Australia and other developed countries, due to large population movements in the twentieth century. Approximately 300,000 severely affected children are born each year with thalassaemia and various other abnormalities of haemoglobin synthesis. If untreated, most thalassaemia patients will die within the first few years of life. The vast majority of thalassaemia patients depend on regular blood transfusions every two to three weeks, and on nightly infusions of an iron chelator (a drug for removing excess iron from the blood). These procedures place considerable burden on thalassaemia patients, their families and society, and expose them to blood transmitted infections. The only curative treatment for thalassaemia is bone marrow transplantation from a matching donor. However, the vast majority of patients do not have matching donors and thus the only prospect for them to receive such therapy is to replace in their bone marrow cells a copy of the normal set of genes for the synthesis of haemoglobin. The studies in this proposal are therefore designed to test gene therapy protocols on bone marrow stem cells derived from thalassaemia patients. A normal set of globin genes will be delivered to the bone marrow stem cells via non-viral delivery systems and examined for function in an immunodeficient mouse strain that can accept human bone marrow. This research may enable bone marrow transplantation to be applied for the therapy of most patients with thalassaemia, while it may also have a major impact on therapeutic approaches for other haematological anomalies.Read moreRead less
Dystrophin Gene Repair In Mdx Mouse Myoblasts And Bone Marrow Cells As A Basis For Autologous Transplant In Human DMD
Funder
National Health and Medical Research Council
Funding Amount
$422,036.00
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 repopulated with genetically corrected cells 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 diseases.Read moreRead less
Myelin Repair By Neural Stem Cells Genetically Modified To Secrete Growth Factors TGFbeta Or IGF-1
Funder
National Health and Medical Research Council
Funding Amount
$199,165.00
Summary
The goal is to locally modify the environment in demyelinating lesions to enhance repair and recovery of function. We will use undifferentiated neural stem (progenitor) cells (NSC) as gene delivery vehicles to supply therapeutic growth factors to areas of damage. Implanted NSC integrate readily into the brain, restoring lost functions, without causing damage. They respond to tissue damage by differentiating into appropriate cells to repair defects, features which are particularly valuable where ....The goal is to locally modify the environment in demyelinating lesions to enhance repair and recovery of function. We will use undifferentiated neural stem (progenitor) cells (NSC) as gene delivery vehicles to supply therapeutic growth factors to areas of damage. Implanted NSC integrate readily into the brain, restoring lost functions, without causing damage. They respond to tissue damage by differentiating into appropriate cells to repair defects, features which are particularly valuable where endogenous myelin repair mechanisms have failed. The first approach will determine whether NSC engineered to secrete Insulin Like Growth Factor-1 (IGF1) promote myelin repair. IGF-1 is a potent stimulator of oligodendrocytes, the myelinating cells in the brain. Itstimulates oligodendrocyte proliferation, differentiation and myelin formation so it may reverse the demyelination and oligodendrocyte loss which are hallmarks of disease. The second strategy is to use NSC to deliver TGF-beta directly to demyelinated areas. TGF-beta suppresses autoimmune responses and is central to recovery from episodes of demyelination in multiple sclerosis and mouse models of immune demyelination. Two mouse models of demyelination will be used to determine the effect of implanted genetically modified NSC; inherited Krabbe disease in which a biochemical defect produces progressive toxic damage to myelinating cells, and injection of an antibody to myelin oligodendrocyte glycoprotein, which induces immune-mediated myelin damage. The behaviour and survival of IGF-1 or TGF-beta secreting NSC, the impact on the quantity of myelin, number of oligodendrocytes and nature of the cellular response to therapy will be quantified. The need for effective therapy of demyelination is urgent. Successful delivery of growth factors to support myelin repair combined with oligodendrocyte replacement would be a significant advance towards treatment for MS, Krabbe disease and other severe neurological disorders.Read moreRead less