Quick Project Snapshot
Overcoming the sprouting limit of axons in the brain - using biomaterials for the treatment of Parkinson's disease
Current pharmacological or surgical therapies for Parkinson’s disease (PD) offer only symptomatic relief. The loss of neurons continues inexorably until the disease reaches its conclusion. Therefore new ways are being explored to prevent ongoing neuronal degeneration and to restore functional pathways. Cell transplantation is a potentially effective treatment strategy for PD. However for the success of this strategy, the implanted neurons must form sufficient and appropriate synaptic connections. A major obstacle to this success is that the adult brain does not i) provide adequate trophic support, resulting in poor engraftment and ii) provide guidance cues that promote growth of new neuronal fibres over significant distances, to restore the hosts neural circuitry. This project builds upon our published and preliminary data and utilises a cross-disciplinary approach, using an injectable hybrid matrix based exclusively on FDA-approved biodegradable biomaterials. The hybrid matrix is designed to assist implanted dopaminergic (DA) neurons to survive and bridge the nigrostriatal neural pathway in the brain, which deteriorate as a consequence of PD. Our research project builds upon recent research findings, which demonstrate that our novel matrix: 1) provides a favourable 3-dimensional cellular microenvironment, 2) has a minimal inflammatory footprint and integrates seamlessly into the brain and 3) provides functional recovery when used in conjunction with DA neurons in a mouse model of PD. We therefore seek to use our cell-matrix construct and demonstrate functional recovery in animal models. Figure text: An injectable matrix is implanted beside the nigrostriatal tract to improve engraftment and provide axonal guidance cues for implanted DA neurons to reach their target. The distance in mouse is 5mm, marmoset 10mm and human 30mm.
Pre-clinical Parkinson’s Disease Research Laboratory
This laboratory focuses on understanding the basic cellular functions and the changes in functions of cells that result in the spectrum of Parkinsonian disorders, such as that occurs in, Parkinson’s disease, Parkinson’s disease dementia and multiple system atrophy. We are particularly interested in the biology of iron and copper in these diseases and how they interact with alpha-synuclein to produce the wide range of symptoms and pathologies observed within these disorders.
In conjunction with Prana Biotechnology we are able to explore novel compounds that have the potential to move towards novel therapeutics. One compound we helped select has completed pre-clinical testing in the laboratory. This compound is undergoing toxicology testing, safety trials in humans for this compound are being planned for the near future.
We utilise a number of techniques within the laboratory, such as in vivo mouse models of disease, animal behaviour, aseptic surgery, microdialysis, multi-electrode arrays for electrophysiology, cell culture (primary cultures, cell lines), western blot, advance microscopy and histological work (stereology) utilising both animal and donated human tissues. The overall aim of this laboratory is to use the cellular knowledge of Parkinsonian disorders to development new therapeutic directions.
PhD student projects are available.
This Laboratory is currently supported by: NHMRC, ARC, Prana Biotechnology, MJ Fox and Shake it up Foundation, Parkinson’s UK and has strong ties with Parkinson’s Victoria.
All Projects by this LabDoes early life exposure to iron represent a risk for Parkinson’s disease?Overcoming the sprouting limit of axons in the brain - using biomaterials for the treatment of Parkinson's disease
Dr Lachlan Thompson
Scientists in the Neurodegeneration division interrogate how neurones live, die and can be rescued to improve brain function in degenerative conditions such as Parkinson’s and Motor Neuron Diseases. There is no effective treatment for Motor Neurone Disease and the incidence of Parkinson’s Disease is rising alarmingly in our aging community. Gene abnormalities, energy deprivation, toxic rubbish accumulation and inflammation all contribute to a toxic environment for brain cells. Our teams study these events in animal models and cultured cells, with a view to translating knowledge into new therapies for human patients.