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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Abdominal muscle stimulation to improve bowel function in spinal cord injury

Bowel complications, resulting from impaired bowel function, are common for people living with a spinal cord injury (SCI). As a result, people with a SCI have high rates of bowel related illness, even compared with those with other neurological disorders. This includes high rates of abdominal pain, constipation, faecal incontinence and bloating. These problems lower the quality of life of people with a SCI and place a financial burden on the health system. A treatment that improves bowel function for people with a SCI should reduce illness, improve quality of life and lead to a large cost saving for health care providers. Bowel problems have traditionally been managed with manual and pharmacological interventions, such as digital rectal stimulation, enemas, and suppositories. These solutions are usually only partially effective, highlighting the need for improved interventions. The abdominal muscles are one of the major muscle groups used during defecation. Training the abdominal muscles should improve bowel function by increasing abdominal pressure. During our previous Abdominal FES research with people with a SCI, we observed that Abdominal FES appeared to lead to more consistent and effective bowel motion. However, this evidence remains anecdotal. As such, we are going to undertake a large randomised controlled trial to investigate the effectiveness of Abdominal FES to improve the bowel function of people with a SCI. This study will make use of a novel measurement system (SmartPill, Medtronic) that can be swallowed to measure whole gut and colonic transit time. We will also assess whether Abdominal FES can change constipation-related quality of life and the use of laxatives and manual procedures, as well as the frequency of defecation and the time taken. A positive outcome from this study is likely to lead to the rapid clinical translation of this technology for people living with a SCI.