Meet the team behind the GDNF trial
Can GDNF treatment slow, stop or reverse the course of Parkinson’s? That’s the question a team made up of researchers, charities, companies and people with Parkinson’s set out to answer in a unique and complex clinical trial.
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GDNF (glial cell line-derived neurotrophic factor) is a special protein that is naturally produced inside the brain and supports the survival of many types of brain cells — including the cells lost in Parkinson’s.
To investigate the effects of GDNF, 41 people with Parkinson’s took part in a groundbreaking clinical trial in Bristol.
In the first phase, participants received either GDNF or a placebo (a dummy drug) for nine months. Neither the researchers nor the participants knew who was receiving what, which is why this kind of study is called ‘double-blind’. In the second phase all participants received GDNF for a second nine months.
The study came to an end in February 2017 and the full analysis of the results is now well underway. Initial results suggested that GDNF treatment is safe but didn’t show a clear cut difference between participants who received GDNF compared to those who received a placebo.
Dr Alan Whone, a consultant neurologist and researcher based at Southmead Hospital in Bristol, is the Chief Investigator and leader of this ambitious study. Alan says:
“When we sat down to put together the plan for this clinical trial back in 2011, I knew this study would be the most complex and challenging I had ever been involved in — but also the most exciting. A study of this magnitude would usually be carried out across multiple hospitals and sometimes in multiple countries.
“So the fact that we’ve managed to take such a large group of people with Parkinson’s through this study at just one hospital is a fantastic achievement.
“It’s all been down to incredible teamwork across a huge range of different groups and I feel very proud to be part of such an amazing collaborative effort.”
Meet the team who’ve made the trial possible
The company providing GDNF
MedGenesis is a Canadian biotechnology company founded in 2006 to develop new therapies for serious neurological conditions. MedGenesis own the rights to GDNF and have supplied the drug for this trial for free.
They have also brought their professional expertise to support the study, as Chief Operating Officer Lara Longpre explains:
“So far in the studies we have done more than 600 infusions of GDNF and completed over 500 assessments, generating over 20,000 individual sheets of data.
“My role is to provide project management so that Alan and his team can concentrate on the participants. This means keeping track of all the different tasks and activities, and working with all the partners to make sure everything gets done on time and to the required standards. I’ve worked on many clinical trials, but this one has been one of the most challenging for a couple of reasons. There are multiple parties involved, all based in different places and each with a critical role, so communication has been one of the things we’ve had to focus on.
“The second challenge has simply been the sheer volume of data that we are collecting. Gathering it all, making sure every piece is captured correctly and then figuring out what it means through statistical analyses is a huge task. Although it has been a complex and demanding study, it’s been a wonderful experience and I’m proud of what we’ve achieved together.”
An innovative drug delivery system
To get GDNF to the brain cells that need it, we’re using an innovative delivery system, specially designed for the task.
Paul Skinner is an Operations Manager at Renishaw, the engineering company based near Bristol that has been contributing to the development of the system designed by Professor Steven Gill. Paul says:
“As a company we specialise in developing systems that do complex tasks with extreme precision. In the trial we have worked closely with the hospital and lead surgeon, Professor Steven Gill, who designed a system that can deliver GDNF safely, accurately and consistently to the right parts of the brain.
“Participants had four tubes carefully placed into their brains that are connected to a small port behind their ear. This device allows GDNF to be pumped directly through the tubes to the affected brain areas with pinpoint accuracy.
“First we use brain scans to build a 3D map of each participant’s brain. This allows the surgeons to plan the safest route for implanting the device. Our specialised robot is then programmed to guide the surgeons to implant the device during the surgery.
“This is the first time this kind of delivery system has been shown to deliver drugs successfully. It has exciting possibilities for other brain conditions, which we’re already exploring.”
A dedicated team in Bristol
A team of 10 doctors, nurses and administrators at the Brain Centre at Southmead Hospital in Bristol are involved in carrying out the study.
Here we talk to Louise Hawkins, the Clinical Trial Manager, about her role:
“My role is to make sure the day-to-day running of the study all goes smoothly. This means everything from making sure the pharmacy provides us with all the GDNF or placebo we need, through to arranging all the participant appointments, travel expenses to be paid and managing the budget. “On a typical week we’ll have 14 of the participants visiting the hospital for assessments and infusions, and co-ordinating all of that requires a lot of teamwork and communication.
“I’ve been working in the NHS for 13 years and I’ve been involved in running studies for the last seven. This study is the most complex and interesting I’ve ever been involved with. It’s been great to develop such good working relationships with all the other partners. “Without a doubt the best part of my job is the participants. They’re a lovely bunch of people who are all so committed to finding a solution to this terrible condition. If they come away from the study having had a positive experience then I’ll be happy that we’ve done our job well.”
41 incredible participants
Groundbreaking research relies on people who courageously volunteer to participate. Taking part in this study is particularly demanding as it involves complex brain surgery, frequent visits to Bristol for treatment and detailed assessments, as well as undergoing brain scans.
Christine Proctor is one of the 41 participants, and here she shares her highs and lows from life on the trial.
“In early 2015 I was accepted as a participant on the GDNF trial. Although part of the rigorous screening process included talking through all the potential psychological, physical and emotional consequences. Without doubt participating in this study has challenged me to my limits.
“Completing physical assessments every eight weeks while I’m off my regular medication for 24 hours is like climbing Everest, and it’s why they call studies like this one a trial.
“But the positives far outweigh the challenges. The nicer things are meeting the wonderful and committed people involved in the study. Although it involves a 500 mile round trip, I look forward to my monthly visit to have my infusion. It’s a very relaxed procedure during which I can enjoy a snack, read my newspaper and chat with other participants and the research staff. I have learned a lot about my Parkinson’s and whatever the results ultimately tell us, I feel privileged to have been able to contribute to this study.”
A way to see into participants brains
All the participants involved in the trial are undergoing detailed brain scanning.
Professor Chris Marshall, Director of the Wales Research and Diagnostic PET Imaging Centre at Cardiff University, says:
“My role in the study is to manage the brain imaging. We’re using a type of brain scanning called PET imaging to measure how dopamine is used inside the brains of the participants. Participants have an injection of a radioactive version of dopamine and lie as still as possible in the scanner for 90 minutes. The PET scanner allows us to track the movement of the radioactive dopamine through the participants’ brains.
“One of the most technically challenging parts of this project was actually manufacturing the radioactive dopamine. To make enough of it to do all the scanning we’ve had to develop an innovative new production method which took us nine months to get up and running. We can now make around 100 times the amount of radioactive dopamine than using the previous method, which is extremely exciting. We’re the first in the UK to achieve this and I believe it’s going to open up huge opportunities for future Parkinson’s research studies.”
Once Chris and his team have taken the brain scans in Cardiff they pass them on to Professor Vesna Sossi and her team at the University of British Columbia in Canada for analysis. Vesna explains:
“When we receive the images to analyse they are completely anonymous. We don’t know which participant they are from, or whether they are receiving GDNF or a placebo. This is really important because it means we can analyse them without being biased in any way.
“This type of brain imaging is tremendously powerful for helping us to understand the effects of treatments like GDNF. The radiotracer we’re using helps us zoom in to see what is happening to dopamine inside the brain — and whether there are any changes in the rate at which it is made or stored — which would otherwise be totally impossible.”
Two charities with a shared mission
All research relies on funding and the GDNF trial is funded by Parkinson’s UK, with crucial support from The Cure Parkinson’s Trust. The two charities have between them provided £2.5million to support this crucial project, as well as helping to raise awareness of the study and supporting the participants.
Dr Arthur Roach, Director of Research at Parkinson’s UK, comments:
“The GDNF trial is one of the most important studies Parkinson’s UK has ever supported. The scale of collaboration involved in this project is really unprecedented and just goes to show what can be achieved when companies, charities, patients and researchers work together.”
Helen Matthews, Chief Operating Officer at The Cure Parkinson’s Trust, adds:
“This trial has fostered a fantastic sense of teamwork between the scientists, clinicians and those participating in the trial. Above all else it has demonstrated the importance of effective communication between all parties and the value of uniting everyone involved. We hope that this innovative way of working forms a template for other trials in the future.”
This ground-breaking trial is the subject of a fantastic two-part documentary series for BBC Two — The Parkinson’s Drug Trial: A Miracle Cure? The first part will be aired on Thursday 28 February at 9pm.
