NeuRA Magazine #20


Dr Nicolas Dzamko works with Prof Glenda Halliday to understand the causes of Parkinson’s disease. He has recently published two landmark studies that provide hope for early detection and possible treatment of Parkinson’s disease. He tells us more about the two studies.

Your first study has looked at one of the key causes of Parkinson’s disease. What did you find?
We modelled the early stages of Parkinson’s disease so we could gain a better idea of its causes and a possible treatment. This is the result of four years’ worth of work, and we’re really excited by the study’s outcomes. We’ve shown how inflammation within the brain is related to the development of Parkinson’s disease, and we’ve identified a potential mechanism that can prevent this inflammation. This gives us a new target for therapeutic research, which we’re now working on.

You’ve used a new approach for this study. Tell us about that.
This is the first time we’ve used the human-induced pluripotency stem cell model. This was the Nobel-prize winning discovery from a couple of years ago and we’ve got it up and running now, so we can take someone’s skin cells, turn them into brain cells and study them in a dish.

One of the key causes of Parkinson’s is the accumulation, or ‘clumping’, of α -synuclein in the brain, which causes a loss of cells and eventually leads to the symptoms of Parkinson’s. You were able to stop that process in your study.
Yes, that’s what we were able to do. We could activate the inflammatory pathways, see the α -synuclein clumping and introduce drugs in order to stop that from happening. Given that we were able to find this association in the post-mortem brain tissue, then model this relationship in tissue culture, we’re confident that we’ve understood a key process in the development of Parkinson’s.

What happens next?
The next stage will be to identify a drug that can be used in human trials, which acts on the pathway we’ve identified and prevents the increase in α-synuclein.

You’ve been working on a second study that has found a possible early indicator of Parkinson’s, is that correct?
We conducted one of the largest post-mortem brain studies in the world, and confirmed that a protein (LRRK2) associated with the development of Parkinson’s disease is increased in the pre-symptom stages. This leads us to believe that we may be able to treat Parkinson’s disease sooner.

What is the LRRK2 gene?
This is a gene that is found in people with a family background of Parkinson’s disease and is a known genetic contributor. The study found that there are increased levels of LRRK2 in the pre-symptomatic stages of Parkinson’s, suggesting that this may be an appropriate time to administer pharmaceutical therapies. Previous studies have shown that Parkinson’s-associated genetic mutations increase the activity of LRRK2, and that this activity can be reduced by drug therapies.

How did this collaboration come about?
The Michael J Fox Foundation got in touch with Prof Glenda Halliday and myself because we have access to brain tissue. We collaborated with the who’s who in the world of studying post-mortem brain tissue. Most of these types of studies use a sample size of eight to 12 brains. We’ve got up to 30 for each of our groups and we’ve studied not just one part of the brain, but several parts of that brain that are affected differently in the disease. So we have a really comprehensive picture of what is happening with the LRRK2 protein.


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LEAD!- Leveraging Evidence into Action on Dementia

Currently, there is no effective treatment for dementia, highlighting the urgent need to preventing more cases through evidence-based strategies for risk reduction. As there is an overlap between the risk factors for dementia and other preventable non-communicable diseases including stroke, diabetes, and heart disease, it is important to build upon proven risk-reduction strategies. What is LEAD? LEAD! is a project funded by the NHMRC Boosting Dementia Research Grant led by Professor Kaarin Anstey. It involves an international collaboration between leading academics, clinicians, consumers, and community members. Organisations involved include the Department of Health, WHO, Dementia Australia, Alzheimer’s Disease International, Diabetes Australia, and Heart Foundation. The project aims to translate dementia research and implement evidence-based strategies for dementia risk reduction to individuals, communities, and healthcare centres. Three workstreams The project has three concurrent workstreams over five years: Development, Implementation, and Evaluation and adoption. The Development stream, led by Professor Kaarin Anstey and Associate Professor Peters, focuses on building a new tool for predicting dementia and other non-communicable diseases including stroke, diabetes or myocardial infarction. The tool will be available to the public, researchers and clinicians. It will save clinical assessment time, accurately predict multiple outcomes and will be more acceptable in comparison to using individual tools for each disease outcome. The Implementation stream led by Professor Nicola Lautenschalger’s team at the University of Melbourne, will develop strategies to support the implementation of dementia risk reduction evidence by engaging with consumers, clinicians, policy makers, and the public. The stream will develop strategies for incorporating the new risk assessment tool into various technological platforms (e.g., websites or apps). The Evaluation and adoption stream, led by Professor Anstey and in collaboration with Professor Louisa Jorm and Dr Heidi Welberry at UNSW, focuses on measuring trajectories of Australian’s national risk factor profiles for multiple chronic diseases. Collaboration with key stakeholders including the WHO will help build an evaluation framework and methodology for implementing evidence on dementia risk reduction based on WHO guidelines at national level and in the global context.