Charged Lipophilic Dendrimers: Delivery Of Oligonucleotides With Therapeutic Potential
Funder
National Health and Medical Research Council
Funding Amount
$422,036.00
Summary
Choroidal neovascularisation, which is the most severe form of Age Related Macular Degeneration (AMD) is the major cause of blindness in the developed world. The disease usually affects people above the age of 75-80. With an ageing population, reaching 3.5 million (over 65) in Australia by year of 2020, AMD is quickly becoming a significant socio-economic problem. Gene therapy could be a cure for the above disease. Currently, there are large numbers of antisense oligonucleotides that have the po ....Choroidal neovascularisation, which is the most severe form of Age Related Macular Degeneration (AMD) is the major cause of blindness in the developed world. The disease usually affects people above the age of 75-80. With an ageing population, reaching 3.5 million (over 65) in Australia by year of 2020, AMD is quickly becoming a significant socio-economic problem. Gene therapy could be a cure for the above disease. Currently, there are large numbers of antisense oligonucleotides that have the potential to be developed as new medicines. However, a lack of absorption-cellular uptake and poor in vivo stability are major hurdles that must first be overcome, before any of these compounds will reach the clinic. Synthetic DNA delivery agents are of interest for gene therapy as an alternative to viral vectors, since they carry potentially fewer risks in terms of immuneresponse and propagation. Gene transfer with synthetic compounds is a growing field of research and the largest family of such agents is based on positively charged lipids which are able to self-associate and to form complexes (salts) with DNA conferring a compacted state on the plasmid. Our project will address these major issues through a highly novel strategy involving ion pair formation of lipophilic dendrimer (tree-like compounds with positive charges on the surface) constructs. This multidisciplinary approach has the potential to develop and test new DNA-dendrimer complexes and test them in a well established animal model for neovascularisation. Successful completion of this project might offer a potential therapy for choroidal neovascularisation, with a good chance of entering into human clinical trials by year 2004.Read moreRead less
The Blood-Retinal Barrier - Modelling Mechanisms For Maintenance, Breakdown And Repair
Funder
National Health and Medical Research Council
Funding Amount
$394,310.00
Summary
We believe that breakdown of the barrier that separates the delicate nervous tissue of the eye from the bloodstream, the blood-retinal barrier, may be an early event in the development of age-related macular degeneration (AMD), now overall the commonest cause of blindness in Australia. We have recently demonstrated with the first scientific clinical trials to be conducted in the world that an injection of steroid into the jelly of the eye, or vitreous , of the steroid triamcinolone slows the gro ....We believe that breakdown of the barrier that separates the delicate nervous tissue of the eye from the bloodstream, the blood-retinal barrier, may be an early event in the development of age-related macular degeneration (AMD), now overall the commonest cause of blindness in Australia. We have recently demonstrated with the first scientific clinical trials to be conducted in the world that an injection of steroid into the jelly of the eye, or vitreous , of the steroid triamcinolone slows the growth of abnormal blood vessels in patients with wet AMD. In the current project, Prof Nick King, a cell biologist and viral immunologist, will collaborate with Dr Michelle Madigan, A-Prof Jan Provis, both experts in experimetnal AMD, and A-Prof Mark Gillies, a clinician-scientist specialising in AMD, to study how the treatment works using established animal and laboratory models of a damaged blood retinal barrier. We will be particularly interested in processes which are thought to critical in the development these diseases. We will also study newly described processes by which the junctions that seal the cells of the barrier together come apart. We will be interested not just in the cells that make the barrier, but also the effect of nearby cells that are thought to contribute to it. These studies will provide a solid foundation for the rationalisation of steroid treatment for AMD which can be expected to result in improved outcomes for our patients. The studies may also provide insights into how other barriers malfunction, such as the blood brain barrier which breaks down in Alzheimer s disease and multiple sclerosis.Read moreRead less