Stage II In The Development Of Eph/ephrin Based Tumor Targeting Reagents: Optimisation Of Drug Efficacy And Delivery
Funder
National Health and Medical Research Council
Funding Amount
$204,125.00
Summary
In the final stage of cancer, including melanoma, tumor cells gain the ability to spread, a process called metastasis. Altered communication between cancer and normal cells is one of the causes of this invasive characteristic. We have started the development of novel agents that target and modulate proteins on the cell surface that control these properties and are found in metastatic tumors. We propose to refine the targeting and killing properties of these agents for early clinical testing.
The proposed project is part of a research programme aimed at developing a new drug to reduce the side effects of cancer radiotherapy. These side effects result from the radiation damage to normal tissues close to the tumour. Since in many instances the normal tissues at risk are accessible to topical application (eg. skin in breast cancer patients, rectal mucosa in prostate cancer patients, oral mucosa in all patients being treated for tumours in the head and neck region) the concept is very si ....The proposed project is part of a research programme aimed at developing a new drug to reduce the side effects of cancer radiotherapy. These side effects result from the radiation damage to normal tissues close to the tumour. Since in many instances the normal tissues at risk are accessible to topical application (eg. skin in breast cancer patients, rectal mucosa in prostate cancer patients, oral mucosa in all patients being treated for tumours in the head and neck region) the concept is very simple. A drug which makes cells less sensitive to X-rays (these drugs are called radioprotectors) is simply applied topically to the normal tissues at risk. For this purpose, we have developed a new radioprotecting drug called methylproamine which is 100-fold more potent than previously-developed radioprotectors. Unfortunately, methylproamine is not suitable for our purpose because at higher concentrations it is toxic to some cells. This hurdle must be overcome in order to make the project attractive to potential commercial sponsors. Our aim is to modify methylproamine by removing the molecular features that cause the cytotoxicity. We have established that this is feasible, by synthesising and evaluating a small family of methylproamine analogues. Some less toxic family members have already been identified. With this knowledge, we now propose to use special computer programmes to design a much larger family of methylproamine analogues, and to synthesise and test each one in order to identify the most promising candidate for our purpose. Once the efficacy window hurdle is passed, the subsequent milestones to commercialisation and clinical implementation can be addressed, with appropriate sponsorship. An Australian company has already expressed strong interest and is evaluating the opportunity.Read moreRead less
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