‘Our volunteers can make such a difference’

Dr Caroline Williams-Gray is a clinical lecturer and junior research group leader at the John Van Geest Centre for Brain Repair. She is looking at whether the immune system has a part to play in the progression of Parkinson’s disease.

Caroline, tell us about your work…

My area of research is Parkinson’s disease, and my post allows 50% dedicated research time for my work in this area. The other half of my work is as a practising clinical neurologist for the NHS. The main purpose of my work is to investigate why Parkinson’s disease evolves differently in different people.

If we look at people with Parkinson’s who have been diagnosed at the same time and compare them 10 years later, we find that they will have developed quite different symptoms at different rates. Some individuals may have problems restricted to issues with movement control which can be well managed with medication, whereas others will develop significant memory and balance problems at an early stage in their disease which are much more difficult to treat.

We are investigating the underlying reasons for these differences, by looking into biological variation between individuals with different types of Parkinson’s, and in particular we are looking at variations in their immune responses. We hope that this will ultimately lead us to new ways of treating the disease with therapies targeted at the immune system.

How long have you worked here?

I’ve been in my current post for two years but I’ve been working here in Cambridge for over 13 years. I first came here as a junior doctor in general medicine, and chose to work here because of the reputation of the hospital and the quality of the training offered. In 2004 I took the opportunity to do a PhD in clinical neuroscience in Roger Barker’s lab, and that’s when my interest in Parkinson’s really started. Since the PhD, I’ve been combining specialist training in clinical neurology with my ongoing research work.

What do you do on a day-to-day basis?

Each day is very different. On some days I will be in the lab, working on experiments using blood-derived immune cells from Parkinson’s patients, or examining post mortem brain sections. On some days I’m in research meetings, on other days I will be in the clinic seeing patients. I work in the Parkinson’s research clinic, the Huntington’s disease clinic and also do a general neurology clinic at Cambridge University Hospital. In addition, I supervise PhD students who are working with me on investigating the immune system in Parkinson’s. It’s a very varied role.

What kinds of research are happening here to do with Parkinson’s?

Here at the Centre for Brain Repair there are a number of different projects on Parkinson’s disease, including clinical studies following up large numbers of patients over time to investigate different types of Parkinson’s disease. Studies in the laboratory try to model these different types of disease in cells, and there are studies which are looking for novel ways to treat the disease, including cell transplant therapies.

My own work is currently focusing on the role of the immune system in Parkinson’s and we’re doing this in various different ways. One way is examining post mortem brains for inflammatory changes – some patients have kindly donated their brains to the brain bank after death to help our research. We’re also looking at immune cells in blood samples donated from Parkinson’s patients as well as healthy individuals of a similar age without the disease, to see if we can find any important differences.

Why were you interested in Parkinson’s as an area of research?

I first became interested in Parkinson’s when I was doing my early training in neurology, and was particularly struck by the way the disease behaved so differently in different people. I went on to investigate this further during my PhD, when I looked at a large group of newly diagnosed patients and followed them up over time with detailed clinical and memory tests.

One of the most interesting things that came out of this study was the finding that memory and thinking problems were very common in Parkinson’s. Over the 10 years from diagnosis, nearly 50% of the individuals in the group we were following went on to develop dementia, with a huge impact on the quality of life of both the individuals concerned and their families. Realising memory problems were so important in the disease, I was very keen to try and  understand what the factors are that drive the early development of dementia in some people with Parkinson’s – this should ultimately guide us in terms of developing therapies to slow down this process.

What can be done to treat Parkinson’s?

Many of the early symptoms related to movement problems and stiffness can be treated and managed well with medication that replaces or mimics dopamine, the principal brain chemical that is affected in Parkinson’s. But some of the symptoms that occur a bit later such as balance and memory problems are much more difficult to treat. None of the therapies we currently have to help the symptoms of the disease actually affect the underlying disease process in the brain, which continues to progress over time. There’s an urgent need to develop a therapy that will actually slow the underlying disease process.

Why do you think your research in Parkinson’s is important?

Because if we can establish that the immune system contributes to disease progression, then treatments that target the immune system could be tested in Parkinson’s. Such treatments that target the immune system are already available and used for other conditions, so we could adapt these to use in Parkinson’s relatively quickly, whereas creating a brand new drug takes much longer. So this work has the realistic prospect of leading to new therapies to modify the course of Parkinson’s disease within a short time frame.

How long will this research take to help people with Parkinson’s?

I hope we will be in a position to start a trial of immune-based therapies in Parkinson’s disease locally within the next three years. Larger multicentre trials would then have to be undertaken before any new therapy was licensed however, this would take a few more years.

Is it only people with Parkinson’s that can help you with your research?

The work I do is very much centred around the patients who come to our research clinic and we couldn’t do our work without them. But we also need people without Parkinson’s to volunteer to act as ‘controls’ so we can compare their characteristics. We have been fortunate that a number of individuals from the community have volunteered to help in this way. We also work with the National Institute for Health Research (NIHR) Cambridge BioResource which has a large database of volunteers, including patients with various medical conditions as well as healthy individuals who have provided DNA for genetic testing. This is a fantastic resource and gives us the opportunity to match people without Parkinson’s to our patients in terms of their genetic characteristics, which is really important for some of our studies.

Why should people take part in research?

In our ageing society, neurodegenerative diseases are becoming an increasing problem, and we currently have no way of slowing down their progress. It’s imperative that we try to develop new therapies to modify the course of these diseases, and we couldn’t make any progress without the involvement of our volunteers.

People can make such a difference by signing up to help with research. Just donating a small sample of blood at the NIHR Cambridge BioResource could be the start to helping us find new treatments for Parkinson’s. Our work is also heavily dependent on people registering with the brain donation scheme. We can find out a huge amount about Parkinson’s by examining pathological changes in the brain after death, particularly when we can combine this with data we have collected from an individual through attendance at our research clinic during their life. We also need to look at the brains of individuals without Parkinson’s so that we can make comparisons between diseased and non-diseased brains, so we would encourage anyone to sign up – it’s such a valuable legacy to research.

To help fight the battle with Parkinson’s, do any of your clinical studies require volunteers to trial a new drug?

Yes, a small proportion of the studies we do here at the Centre for Brain Repair involve taking a new drug. The majority of our clinical research though is observational, looking at how disease develops over time as well as genetic and blood markers that are associated with particular patterns of change. If people want to volunteer for any research, everything is fully explained beforehand and there’s plenty of opportunity to ask questions before you enrol in a study. You are also free to withdraw from research studies at any time, even if you’ve already consented to take part.

How can people get involved in research?

Individuals with Parkinson’s can find out more about getting involved in research via our website. People without Parkinson’s are also welcome to volunteer either with us, or via the NIHR Cambridge BioResource through which they can help with research into many different conditions, not just Parkinson’s. You can find out more about registering as a brain donor at the Cambridge Brain Bank and anyone can do this, not just patients with neurological diseases.

What do you do in your spare time?

Outside of work, I’m a busy mother to 2 young children, and one of my major challenges is trying to maintain a good work-life balance so that I can ensure my family get all the attention they need and deserve.
Weekends generally revolve around taking the children to ballet lessons, swimming lessons, helping with their homework, children’s parties, and other family activities. There’s not much time for relaxation but I wouldn’t really want things any other way.

What would be your dream job?

I would like to continue to develop my career as an academic neurologist, and lead my own research group investigating the factors that determine the clinical differences we see in Parkinson’s patients. I really enjoy my current mix of research and clinical work and hope I can continue to balance the two in the future. My ultimate aim is to be able to directly translate my research findings into new therapies which I can offer to patients in the clinic with the prospect of being able to prevent or at least slow down progression to disabling complications such as balance problems and dementia.

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