NeuRA Magazine #20

DR NIC DZAMKO

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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Brain and Knee Muscle Weakness Study

Why Does Quadriceps Weakness Persist after Total Knee Replacement? An Exploration of Neurophysiological Mechanisms Total knee replacement is a commonly performed surgery for treating end-staged knee osteoarthritis. Although most people recover well after surgery, weakness of the quadriceps muscles (the front thigh muscles) persists long after the surgery (at least for 12 months), despite intensive physiotherapy and exercise. Quadriceps muscle weakness is known to be associated with more severe pain and greatly affect daily activities. This study aims to investigate the mechanisms underlying weakness of the quadriceps muscles in people with knee osteoarthritis and total knee replacement. We hope to better understand the relationship between the changes of the brain and a loss of quadriceps muscle strength after total knee replacement. The study might be a good fit for you if you: Scheduled to undergo a total knee replacement; The surgery is scheduled within the next 4 weeks; Do not have a previous knee joint replacement in the same knee; Do not have high tibial osteotomy; Do not have neurological disorders, epilepsy, psychiatric conditions, other chronic pain conditions; Do not have metal implants in the skull; Do not have a loss of sensation in the limbs. If you decide to take part you would: Be contacted by the researcher to determine your eligibility for the study Be scheduled for testing if you are eligible and willing to take part in the study Sign the Consent Form when you attend the first testing session Attend 3 testing sessions (approximately 2 hours per session): 1) before total knee replacement, 2) 3 months and 3) 6 months after total knee replacement. The testing will include several non-invasive measures of brain representations of the quadriceps muscles, central pain mechanisms, and motor function and questionnaires. Will I be paid to take part in the research study? You will be reimbursed ($50.00 per session) for travel and parking expenses associated with the research study visits. If you would like more information or are interested in being part of the study, please contact: Name: Dr Wei-Ju Chang Email: w.chang@neura.edu.au Phone: 02 9399 1260 This research is being funded by the Physiotherapy Research Foundation.  
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