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Multiple system atrophy

EXTRA INFORMATION

Understanding why and how MSA occurs

WHAT WE KNOW

About our research

Our aim is to define the pathological pathway that leads to MSA and to identify molecular targets for potential treatment strategies for MSA. Our early research has been instrumental in determining the sequence of pathological events in MSA, which is now recognised as myelin dysregulation (abnormal protein redistributions in oligodendrocytes), followed by demyelination and then neurodegeneration and loss of neurons.

The most common disease that is misdiagnosed as Parkinson’s disease is multiple system atrophy, and both diseases abnormally accumulate the alpha-synuclein protein in their brain. The main difference is that in Parkinson’s disease the protein accumulates in neurons, while in multiple system atrophy it accumulates in their supporting cells, the glia. The Halliday laboratory is trying to understand what underlies these differences.

What we know about MSA:

  • Identified large changes in lipid levels that impact on the glial cells involved.
  • Identified that some people have extremely slow disease progression and are now assessing the factors that seem to arrest the disease in these people.
  • Participated in an international study that suggests the alpha-synuclein protein in MSA may have infectious properties that assists with spreading the disease in the brain.
  • Treatment development and clinical trials.
  • Discovered a new lipid receptor (ABCA8) that is involved.
  • Identified genes involved at the cellular level through transcriptomics.
  • Identified how the pathology spreads in the brain.

Current projects

The glia involved in MSA need sufficient energy to effectively work and support neurons. COQ2 is a gene related to energy production in cells and changes in the COQ2 gene increase the risk for MSA; however, very little is known about levels of expression of this gene, or of the associated energy molecule ATP, in the brain of people with MSA. To establish whether COQ2 activity is indeed a contributing factor in the pathology of MSA, we will measure levels of COQ2 gene and protein in multiple regions of the brain of people with MSA. We will also measure how much of the energy molecule ATP is made. This will help us determine the mechanism of how any deficits in the COQ2 gene contribute to the MSA disease process.

It is possible that boosting the function of COQ2 might combat the disease process of MSA. We will test whether treatment with coenzyme Q10, the product of the COQ2 gene, prevents or reduces alpha-synuclein aggregation in the brain. Using a cell model of MSA, we will measure the effects of different doses of coenzyme Q10 on alpha-synuclein production and aggregation. We expect that coenzyme Q10 treatment will prevent or reduce alpha-synuclein aggregation in oligodendrocytes by ameliorating the levels of ATP and of other molecules known to be involved in MSA pathogenesis. If this approach is successful, we will begin initial therapeutic treatment studies using animal models of MSA.

 

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The RESTORE Trial: Immersive Virtual Reality Treatment for Restoring Touch Perception in People with Discomplete Paraplegia

Chief Investigators: Associate Professor Sylvia Gustin, Prof James Middleton, A/Prof Zina Trost, Prof Ashley Craig, Prof Jim Elliott, Dr Negin Hesam-Shariati, Corey Shum and James Stanley While recognition of surviving pathways in complete injuries has tremendous implications for SCI rehabilitation, currently no effective treatments exist to promote or restore touch perception among those with discomplete SCI. The proposed study will address this need by developing and testing a novel intervention that can provide touch restoration via the primary source of sensory perception: the brain.Complete spinal cord injury (SCI) is associated with a complete loss of function such as mobility or sensation. In a recent discovery we revealed that 50% of people with complete SCI still have surviving somatosensory nerve fibres at the level of the spine. For those with complete SCI this is hopeful news as it means -- contrary to previous belief that communication to the brain had been severed by injury -- that the brain is still receiving messages. This new SCI type is labelled “discomplete SCI” -- a SCI person who cannot feel touch, but touch information is still forwarded from the foot to the brain. The project will use virtual reality (VR) in a way it has never been used before. We will develop the first immersive VR interface that simultaneously enhances surviving spinal somatosensory nerve fibres and touch signals in the brain in an effort to restore touch perception in people with discomplete SCI. In other words, immersive VR is being used to re-train the brain to identify the distorted signals from toe to head as sensation (touch). For example, participants will receive touch simulation in the real world (e.g., their toe) while at the same time receiving corresponding multisensory touch stimuli in the virtual world (e.g., experiencing walking up to kick a ball). This project is the first effort worldwide to restore touch sensation in 50% of individuals with complete injuries. The outcomes to be achieved from the current study will represent a cultural and scientific paradigmatic shift in terms of what can be expected from life with a spinal cord injury. In addition, the project allows potential identification of brain mechanisms that may ultimately represent direct targets for acute discomplete SCI rehabilitation, including efforts to preserve rather than restore touch perception following SCI. RESTORE consolidates the expertise of scientists, clinicians, VR developers and stakeholders from NeuRA and UNSW School of Psychology (A/Prof Sylvia Gustin, Dr Negin Hesam-Shariati), John Walsh Centre for Rehabilitation Research, Kolling Institute and University of Sydney (Prof James Middleton, Prof Ashley Craig and Prof Jim Elliott), Virginia Commonwealth University (A/Prof Zina Trost), Immersive Experience Laboratories LLC (Director Corey Shum) and James Stanley. If you are interested in being contacted about the RESTORE trial, please email A/Prof Sylvia Gustin (s.gustin@unsw.edu.au) and include your name, phone number, address, type of SCI (e.g., complete or incomplete), level of injury (e.g., T12) and duration of SCI (e.g., 5 years).
PROJECT