Biological, Functional And Radiographic Evaluation Of Autologous Chondrocyte Implantation
Funder
National Health and Medical Research Council
Funding Amount
$307,400.00
Summary
We will test the hypothesis that autologous chondrocyte implantation (ACI) and extensor realignment produces superior clinical, biological and radiographic results when compared with conventional treatment of realignment and debridement. We will specifically address the following aims: 1. Quantify the clinical outcome of ACI compared to the traditionally used treatment of debridement through the use of functional evaluation in a blinded randomised controlled clinical trial; 2. Evaluate the radio ....We will test the hypothesis that autologous chondrocyte implantation (ACI) and extensor realignment produces superior clinical, biological and radiographic results when compared with conventional treatment of realignment and debridement. We will specifically address the following aims: 1. Quantify the clinical outcome of ACI compared to the traditionally used treatment of debridement through the use of functional evaluation in a blinded randomised controlled clinical trial; 2. Evaluate the radiographic changes in the patellofemoral joint that occur as a result of ACI, using high resolution magnetic resonance imaging (MRI) to quantify the regeneration of hyaline articular cartilage; 3. Using the new technique of confocal arthroscopy, we will compare the histologic appearances of the ACI graft and its interface with adjacent articular cartilage; 4. Evaluate patient, surgical and explant chondrocyte characteristics in relation to functional, radiographic and biological outcomes. With respect to the matrix-induced autologous chondrocyte implantation (MACI) technique, we wish to clarify the clinical practice as a definitive treatment for articular cartilage defects. This will be the first randomised, controlled clinical trial of the MACI technique compared to that used by other groups. A positive clinical outcome from this trial will help promote the three cornerstones of this procedure – successful cell culture, efficient surgical procedures, and complimentary postoperative rehabilitation. Furthermore, this research will: a) Enhance the expansion of the MACI technique; b) Encourage development of endoscopic techniques of implantation using a combination of – • Preoperative defect registration with MRI • pre-cut custom patches, implanted with • Computer-assisted navigation techniques: c) Increase the potential to cater for a larger number of patients requiring articular cartilage repair; d) Confirm the long-term durability of regenerated cartilage in the 4th year and beyond; e) Add further commercial value by demonstrating MACI may prevent the onset of osteoarthritis.Read moreRead less
Development Of A New High Throughput Screen For Drug Binding To HERG K+ Channels
Funder
National Health and Medical Research Council
Funding Amount
$351,320.00
Summary
Inadvertent drug block of hERG, a potassium channel in the heart, can cause cardiac arrhythmias and sudden cardiac death. Screening for hERG toxicity has become a major hurdle for development of new drugs. We will use a mutant hERG protein that has enhanced drug binding to develop a high throughput test for hERG toxicity. Identification of dangerous drugs early in the drug discovery process will save the pharmaceutical industry millions of dollars in the costs of brining new drugs to market.
Prevention Of Neuron Death By Targeted Gene Delivery
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
Neurotrophic factors are potent proteins that have the ability to keep nerves alive. They have therefore been used in clinical trials to treat motor neuron disease, but without success. A major reason for this appears to be the way in which the neurotrophic factors are delivered. Direct injections into the blood stream are a convenient way of getting these large proteins into the bloodstream, but this is not their normal mode of action. These proteins are normally provided by cells adjacent to t ....Neurotrophic factors are potent proteins that have the ability to keep nerves alive. They have therefore been used in clinical trials to treat motor neuron disease, but without success. A major reason for this appears to be the way in which the neurotrophic factors are delivered. Direct injections into the blood stream are a convenient way of getting these large proteins into the bloodstream, but this is not their normal mode of action. These proteins are normally provided by cells adjacent to the nerves. We have designed a system that more closely resembles this physiological mode of action which involves the delivery of neurotrophic factor genes, via the bloodstream, to the affected nerves. Once inside the nerves the factors are produced on site and, following their secretion, act locally and directly on the injured nerves.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
In Vitro And In Vivo Assessment Of The Funhaler -an Innovative Therapeutic Device For Children
Funder
National Health and Medical Research Council
Funding Amount
$472,750.00
Summary
Aerosol therapy is the most effective form of treatment for children with respiratory diseases such as asthma. While optimising aerosol delivery systems has an important role in increasing the efficacy of asthma therapy, ensuring patient compliance is often the most difficult part of the clinician's role, particularly in the paediatric age group. An innovative small volume spacer device (Funhaler) developed by a West Australian company (InfaMed, Ltd) may help overcome this problem. The Funhaler ....Aerosol therapy is the most effective form of treatment for children with respiratory diseases such as asthma. While optimising aerosol delivery systems has an important role in increasing the efficacy of asthma therapy, ensuring patient compliance is often the most difficult part of the clinician's role, particularly in the paediatric age group. An innovative small volume spacer device (Funhaler) developed by a West Australian company (InfaMed, Ltd) may help overcome this problem. The Funhaler incorporates a spinning toy attached to the outside of the spacer. The toy is activated when the patient breathes through the spacer. The device has been designed to encourage children to co-operate when their asthma therapy is being delivered. The Funhaler is currently in the late development stage. We propose, firstly, to carry out in vitro assessments of drug delivery from the Funhaler compared to the two most widely available small volume spacers: the Aerochamber Plus (Trudell, Canada) and the Breath-A-Tech (Scott-Dibben, Australia). These assessments will be carried out to meet the standards of regulatory bodies worldwide (including the FDA). Secondly, we propose to perform extensive in vivo studie: filter studies to assess drug delivery to the patient; deposition studies to measure drug deposition in the lungs; and a pilot clinical trial to assess the efficacy of the device during medium to long-term use in children aged 2-8 years.Read moreRead less