Neurology Central, speaks to Dr Arthur Roach, Research and Development Director at Parkinson’s UK – the largest charity funder of Parkinson’s disease research in the UK – about recent progress and current challenges involved in Parkinson’s research. In particular, we discuss the status of the anticipated glial cell-derived neurotrophic factor study (GDNF) , which investigates whether the growth factor GDNF is capable of restoring dopamine-producing brain cells, and thus slow the course of Parkinson’s.
What are your roles and responsibilities as the Research and Development Director at Parkinson’s UK? How do you split your time between your various responsibilities?
The Parkinson’s UK research group receives approximately 20% of the total Parkinson’s UK budget, so 80% gets spent on different areas such as education and providing direct support to individuals with Parkinson’s and then approximately 20% goes towards the research.
The Research and Development Group decides where that should be spent in order to achieve the best impact for individuals with Parkinson’s, and to deliver the kind of things our members and supporters are looking for. This can include managing our existing programmes – we have certain standard programmes, such as research grant funding for university investigators – as well as thinking about new directions and new programmes we should put in place.
The field is moving, the charity sector is moving, the drug discovery field is moving, so we’re keeping up with that and looking for the new opportunities and areas we should get into. Any new area we enter will often involve developing new types of expertise inside the charity, such as a new way of thinking within our management and Board of Trustees. There’s also the business-as-usual responsibilities, such as administering the grants and reviewing the science that we’re supporting, and then looking at new programmes and new directions.
What are the main focuses for the Parkinson’s UK research team at present?
Probably the majority of our funding today goes towards research into the basic mechanisms underlying Parkinson’s, such as what goes wrong in the brains and the cells of patients with the disorder with an aim of better understanding the fundamentals. This research will allow us to design totally new treatments that can transform the experience of people with the disease and could even lead to a cure. That is probably the main focus of activities today, but we also realize that this has to be updated, unfortunately the basic research is probably at least 10–15 years away from new treatments, and many of the projects that we start at that early stage may have a low probability (certainly less than 10%, but I sometimes use a much lower number) of actually turning into a treatments. So, if we want to work in that area we’ll actually be far away from delivering new treatments.
The second part of the focus is this area is of finding ways to work that are closer to new treatments, that will get drugs onto the market and into patient’s hands in years rather than decades. We’re working out ways to work with all the partners who have been involved and that includes companies, which we haven’t worked a lot with in the past, it includes regulators, and government regulators who approve the drugs. So we’re working at all these levels, and that’s a bit new to us.
Could you update us on the progress of the GDNF trial? Is this the research project that currently holds the most promise for slowing down the course of Parkinson’s?
I personally believe it is the most promising project out there right now. The treatments we have today do a good job in the early stages of the disease, addressing the symptoms on an hour-by-hour, day-by-day basis, but unfortunately the disease is still progressing in the background. Degeneration is still occurring, nerve cells are still dying, and eventually patients get to the stage where even the drugs we have today that treat the symptoms are no longer good enough because so many nerve cells have died. This is a project to not only save those nerve cells from dying, but to look at the ones that are still there, to give them a boost, if you like, to give them more energy, more connections so they can do more of the job and take over from the cells that have already been lost. It’s very promising.
It’s a very difficult trial technically; moreover, it’s taking place in just one hospital center, which is also unusual. Its involves a very special surgery and some very special equipment, so it’s being done in just one center for that reason, but that makes it more difficult to run the trial because we need a lot of patients to come to that one center. However, we’ve been very active on that – we’re pleased that we have found all the patients that we need for that study and now it’s ongoing.
It’s an agent that has been tested in the past using, we think, suboptimal methods of delivery and suboptimal study designs, therefore it’s unclear whether it’s going to work as well as we hope it will. This is the definitive trial, probably the last chance for this particular molecule to investigate whether it works well when tested in the best way, so that’s a very exciting one.
When are we likely to see the results from that trial?
In about a year from now we should see the results and know whether it’s working the way we hoped it would. The trial is small, and because it’s an early stage trial – with very special patients – you don’t want people to over interpret the results of that trial. A good result for this trial would be that it becomes the door that opens into another larger, more definitive, and more expansive study. In about a year we should hear if the results are positive, which is very encouraging but it still wouldn’t be at the stage where it’s ready to be used by a large number of patients; however, it’s an essential step to get there.
What are some of the challenges you face when deciding which research projects to support at Parkinson’s UK? And how do you overcome these challenges?
I think probably the biggest challenge for me is that the early stage research is far from the clinic. If we knew the one thing to work on that would lead to a cure it would be much simpler, but we don’t. This means we have to try a lot of things at an early stage; things that are helping us understand the disease, but perhaps in many cases will not actually lead to a treatment. We have to understand this aspect of the disease, but we’re unable to know for certain which one is going to be the ultimate successful treatment, which is probably the most difficult stage.
In order to do that we don’t actually make those decisions ourselves, we have an expert panel of external researchers from universities not only in the UK, but also in other countries who are immersed full-time in different aspects of Parkinson’s research. They come together, they meet with us here in London, and also work with us via email to evaluate all the interesting project opportunities. They provide a critical review of them, and as a group they arrive at a consensus on where the promising projects seem to be. They prioritize those projects and we listen very closely to the advice of those experts.
Are there any avenues currently being explored that might bring treatments to market more quickly?
A number of research organizations – especially charities like ourselves and some sister charities in the Parkinson’s field – are looking at whether drugs that already exist and are being used for other diseases might now be used for different aspects of Parkinson’s therapy. This is called repurposing or repositioning of drugs. In some ways it’s a shortcut because if these drugs are already being used for other diseases then you save many, many years and probably many, many hundreds of millions of pounds in the cost of bringing those drugs to market.
Ourselves and other charities are looking at ways to exploit that route to bring a potential new treatment to market more quickly. It’s limited because the existing drugs only work by certain mechanisms and therefore they can’t do everything, but I think we’ll also see some drugs that already exist being brought to the Parkinson’s field in perhaps a faster way. We’re involving people with Parkinson’s,the patients are directly supporting us in the search for these new drugs, or these old drugs that can be reused for Parkinson’s. That’s an exciting development to have their involvement so directly in our new research projects.
What do you hope the field of Parkinson’s research will achieve over the next 5 years?
One of my main hopes is that the results from the GDNF study will lead onto a later-stage study in that area. There are some other projects that are of a similar type that could slow the progression of the disease, such as implanted cells, or gene therapy where pieces of DNA are transferred. Those studies are proceeding around the world and we hope they will lead to successful results. In the last 10 years a lot of great work relating to the genetics affecting Parkinson’s has pointed to new potential therapeutic routes and those are going to be investigated and understood.
In 5 years I think we will have well-defined new therapeutic strategies based on the genetics that will point to new treatment methods, perhaps to the next GDNF, or the next promising therapy. In addition we’re seeing more and more international collaboration in research. For example, there are some types of studies that require large numbers of patients or large numbers of certain rare patients, who are hard to find in any one country, so we’re seeing more collaborations where researchers in the UK will work with their colleagues in Europe and the United States to have a more powerful study, and we’ll see more of those in the future as well.
Arthur Roach is the Research and Development Director at Parkinson’s UK. He has over 25 years’ experience directing research in Parkinson’s and other neurodegenerative conditions at universities, hospitals, and pharmaceutical and biotechnology companies.
Arthur is Founder and President of the Geneva PharmaNetwork, and prior to taking up the position of Parkinson’s UK Research Director was Founder and Program Leader at CHORD Therapeutics in Geneva (Switzerland). Prior to this he was Senior Director of Neurodegenerative Research and Disease Area Team Leader for Parkinson’s at Merck Serono (Germany), where his work led to a patent filing for use of safinamide in Parkinson’s. Previous to this Arthur held positions at DuPont Pharmaceuticals Company and Bristol-Meyers Squibb Pharma (NJ, USA), and Allelix Biopharmaceuticals(Canada).
Prior to his career in industry,Roach’s 11 year academic research career included positions at the University of Toronto (Canada) and Cornell University Medical College in New York (NY, USA).
Find out more about Parkinson’s UK research, including how to apply for funding, at parkinsons.org.uk/research. Visit the UK Parkinson’s Excellence Network to access the latest news, resources, events, and training and funding opportunities for health and social care professionals working in Parkinson’s care.
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Future Medicine Ltd.