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Identification Of Novel Regulatory Factors In Midbrain Development To Improve Cell Therapies For The Treatment Of Parkinson’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Cell transplantation is one of the most promising therapeutic strategies for the treatment of Parkinson’s disease. Cells are transplanted directly into the brain of the patient and can compensate for those lost to the disease. In this project we are identifying new genes that regulate the normal development of the transplanted cells in mice. We hope to use this knowledge to improve the reliability and effectiveness of the approach, bringing the therapy closer to the clinic.
Using Stem Cells And Bioengineered Scaffolds To Promote Regeneration Following Necrotic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$710,857.00
Summary
A number of injuries, including stroke, result in tissue loss. Consequently promoting repair will require restoration of tissue structure, replacement cells and a supportive environment to promote integration of these new cells. This study will engineer and develop novel scaffolds that can replace tissue whilst additionally providing physical and chemical support for newly implanted stem cells. This work will be conducted in an animal model of stroke.
If stem cell transplantation is to be useful to repair brain injury, advancement must be made to improve the delivery, survival and differentiation of transplanted cells so that they can sufficiently integrate into the host brain. Here, self-assembling peptides will be developed to provide physical and biochemical support for stem cells and neurones in cell culture (which may be useful for drug discovery) and following transplantation into the injured brain.
Standardising Protocols For The Differentiation And Integration Of Human Pluripotent Stem Cell-derived Neural Transplants In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$987,664.00
Summary
Clinical trials have shown that transplanting dopamine neurons (specific nerve cells) into the brain of Parkinson’s disease patients can improve symptoms. Trials use fetal tissue for implantation, which is unsustainable and highly variable. This proposal will examine stem cells as an alternative. We will establish a reliable protocol to instruct human stem cells to become dopamine neurons, develop methods to select these cells and, examine the integration of these transplanted cells in the brain
Knowledge, Identification And Exploitation Of Dopaminergic Axon Guidance Cues Will Improve Cell Replacement Therapy For ParkinsonÍs Disease.
Funder
National Health and Medical Research Council
Funding Amount
$481,797.00
Summary
Many obstacles exist for cell transplantation in ParkinsonÍs Disease; namely poor graft survival, restoration of appropriate circuitry and adequate nerve fiber growth from new cells. Using knowledge of how neural circuits are established during fetal development, we will attempt to recapitulate these events following transplantation. Further, we will identify new and novel cues in regulating the connectivity and growth of these nerve fibers.
Neogenin: A Regulator Of Neuronal Differentiation And Migration In The Adult Brain
Funder
National Health and Medical Research Council
Funding Amount
$334,053.00
Summary
Conditions such as Alzheimer�s and Huntington�s diseases, as well as stroke, represent a major burden of disease in Australia. One goal of modern neurobiology is to harness the brain's ability to make new neurons so that we can replace those damaged by disease or injury. We will investigate how an important developmental molecule, Neogenin, promotes the production of new neurons in the adult brain. A second goal is to show that Neogenin can be activated to promote the repair of the damaged brain ....Conditions such as Alzheimer�s and Huntington�s diseases, as well as stroke, represent a major burden of disease in Australia. One goal of modern neurobiology is to harness the brain's ability to make new neurons so that we can replace those damaged by disease or injury. We will investigate how an important developmental molecule, Neogenin, promotes the production of new neurons in the adult brain. A second goal is to show that Neogenin can be activated to promote the repair of the damaged brain.Read moreRead less
Neural Transplantation Of Human Bone Marrow Stromal Cells To Replace Oligodendrocytes Lost In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$249,750.00
Summary
Multiple sclerosis is a disease of the central nervous system in which myelin (an insulative coating around the axons of neurons) and oligodendrocytes (the cells that produce myelin) are attacked and damaged by an unknown process. This damage is referred to as demyelination and results in a blocking or weakening of nerve signal conduction. Some of the symptoms of multiple sclerosis are weakness, tingling or numbness of limbs, and double vision or visual loss. One strategy to repair the demyelina ....Multiple sclerosis is a disease of the central nervous system in which myelin (an insulative coating around the axons of neurons) and oligodendrocytes (the cells that produce myelin) are attacked and damaged by an unknown process. This damage is referred to as demyelination and results in a blocking or weakening of nerve signal conduction. Some of the symptoms of multiple sclerosis are weakness, tingling or numbness of limbs, and double vision or visual loss. One strategy to repair the demyelination is to transplant cells into the damaged brain that can replace the damaged oligodendrocytes and remyelinate. Studies have shown that oligodendrocyte progenitor cells and neural stem cells transplanted into the brain can mature into oligodendrocytes and myelinate axons. However these cells are very difficult to obtain, the best source is foetal terminations but the use of such tissue raises ethical and practical problems. Recently cells found in adult bone marrow, called marrow stromal cells, have been shown to differentiate into neural cells when transplanted into the brain. This raises the possibility that sufferers of multiple sclerosis may be able to have marrow stromal cells taken from their bone marrow and then transplanted into their brains to replace their damaged oligodendrocytes. Our study will investigate the differentiation of marrow stromal cells into oligodendrocytes and determine if marrow stromal cells transplanted into demyelinated mouse brain can replace damaged oligodendrocytes and remyelinate areas of damage.Read moreRead less
Pre-Clinical Studies Towards Cell-Based Approaches For Cortical Repair.
Funder
National Health and Medical Research Council
Funding Amount
$739,901.00
Summary
This project seeks to determine whether brain cells that die after stroke can be functionally replaced using cells grown in the laboratory from human stem cells. Current therapies for stroke aim to limit the damage but do not allow for actual recovery of brain function. By growing turning stem cells into specialised cells that match the ones lost after stroke, this project aims to restore motor function by transplanting these cells into the injured brain.
Restoration Of The Nigrostriatal Pathway In The Parkinsonian Brain
Funder
National Health and Medical Research Council
Funding Amount
$299,431.00
Summary
Many obstacles exist for cell transplantation in Parkinson's disease; namely poor restoration of the host brain circuitry due to incorrect graft placement. This results in incomplete motor function and unwanted side effects. Through iterative studies we endeavor to restore this circuitry by placing grafts in the appropriate location and promoting their survival and growth-integrations. This will require: optimizing the donor tissue and exposure of the graft to growth stimulating factors.
This proposal seeks to determine the therapeutic potential of stem cells for the treatment of brain injury early in life, for example as occurs in cerebral palsy. The project will test the capacity of implanted stem cells to both protect the brain and also to functionally replace cells lost to the injury in order to improve motor and cognitive function.