Reflections on the GDNF trial
Three years on, Lesley Gosden, one of 41 participants in the pioneering GDNF clinical trials, shares her reflections on the experience and how she’s channelling her energies into improving future clinical trials.
Diagnosed in 2004, I have lived with Parkinson’s for 15 years and can now barely remember life before.
The GDNF trial was not for the fainthearted, but Parkinson’s is a degenerative condition. It was not going to get better, therefore my future was always going to be a journey into the unknown, but at least this path offered some hope.
My main symptoms at the time were dystonia, mainly in my feet leaving me with very painful cramps and muscle spasms, rigidity and stiffness in my legs and arms and an overwhelming feeling of fatigue. Sleep was always challenging.
A life-changing experience
Participation changed my life in many ways. It took an enormous leap of faith, lengthy discussions with my family and a good deal of soul searching to volunteer my brain for such an invasive and groundbreaking trial. From the camaraderie and continued support still enjoyed with my fellow participants to the tightness and tenderness of my scalp where the delivery equipment was installed and then removed, it is an experience I will never forget.
I have put those I love through a nightmare journey of risky surgery, watching me endure terrifying scans, and facing the psychological effects that a commitment of this magnitude creates. But this just scratches the surface of what they must have experienced. The looks on my sons faces when I left home for further surgery to remove the delivery device told me all I needed to know about how the whole episode had affected them. Once again, they were wondering whether this was the last time they would see their mother.
This has been a long journey punctuated by uplifting highs and shattering lows. But it is a journey we have shared together and it has tightened our bonds as a family.
They have supported me when I have been at breaking point, crawling on the floor with me trying to relieve the excruciatingly painful cramps and muscle spasms that plague my feet and lower limbs following my tortuous experience in the PET brain scanner. They have enthusiastically celebrated the improvements like; being able to take my dog for a walk, driving longer distances, managing the stairs when off medication and generally joining in with family activities where previously I would be sitting on the sideline.
The team at Southmead Hospital, Bristol led by Alan Whone were truly amazing. They felt like a second family and the level of commitment and support exhibited by all team members from the clinicians to the admin staff was exemplary. Despite being a busy clinician Alan got to know us all on a personal level and his dedication to the trial was memorable and very touching. I have continued to consult with him, even though this involves a 150 mile round trip, as I know I am in the best hands.
The end of the trial
My deepest regret is that the trial failed to prove that the treatment worked when it is plain for all around me to see that I have improved immeasurably — GDNF has given me a new lease of life and the effects are still with me.
I went into the project with my eyes wide open — I knew there were no guarantees of success. What I had not prepared myself for was discovering that the treatment worked for me, but remained unproven.
This was a unique trial in many ways and it had a profound effect both physically and mentally. The psychological effects of participating in such an invasive and risky trial cannot be underestimated. The initial realisation that GDNF would no longer be available to me was devastating. I sunk into a deep depression and tried to take stock of my life and my uncertain future.
Today I can reflect on the disappointing outcome and see it in perspective.
We have shown that treatments can successfully be delivered to the relevant part of the brain, proved the safety of the delivery device and thereby enabled operations to help treat children with brain tumours. So that alone makes it all very worthwhile.
I believe that this is not a failure of the drug, but a failure of the tools we have to measure its full effects.
Many tests used to measure symptom severity feel outdated and artificial. How quickly I can open and close my hand is not relevant to my everyday life, but taking the top off a bottle or jar is — yet it is the former that is part of the assessment. Until we have tests that measure effects that reflect what matters to people with Parkinson’s, we’re potentially missing out on beneficial treatments.
Another major issue that I believe we need to tackle is the incredible variability of the condition. I and many others involved in these trials experienced profound benefits, but others didn’t. Why some people respond better to some treatments is a mystery but unless we solve it, again we are setting ourselves up for failure.
Finally, we need to ensure that when trials like this one finish, participants like myself who may be struggling to come to terms with the end of their participation are supported emotionally, or with ongoing medical needs. And we also need to capture the longer term impacts of the treatment. I feel better now than I did before I started the study back in 2015 which suggests the improvements have been sustained — yet these continued benefits are not being captured which is surely a missed opportunity for understanding the full effects of GDNF?
Scientists understand the workings of the brain, however, no-one can truly appreciate the true impact of the condition unless they are living with it day to day. Understanding the wide variation of symptoms and the huge diversity of presentations is essential in the quest for a cure. It is, therefore, absolutely critical to the success of future research that scientists and patients work together to share their knowledge and expertise.
I am determined to channel what I’ve learnt into improving future clinical trials — both to give them a better chance of succeeding and to ensure participants have the best possible experience.
To this end, I have recently become a Patient and Public Involvement volunteer with Parkinson’s UK. I am also a Lay Grant Reviewer, am working on several projects in association with Parkinson’s UK, and talk to new staff joining the charity about living with the condition and my role in research. I am a regular supporter of the fundraising walks for Parkinson’s, as both a participant and a volunteer
So, with hindsight, would I do it all again?
Most definitely yes — in a heartbeat. GDNF gave me a new lease of life, it introduced me to the possibility that there is hope. I am still enjoying the beneficial effects of the infusions as my level of fatigue and mobility has remained improved.
I believe this trial has changed the boundaries and opened up new possibilities. Research has to falter now and again in order to ultimately succeed, and as long as we learn from these disappointments it is all part of the journey towards a better future.
I have tested myself to the limits and grown as a person in the process. I have realised the importance and value of family and friends and gained a renewed sense of purpose in my life.
For anyone considering taking part in a trial, my advice would be to make sure you are fully aware of all the details of the trial from the initial concept, through the methods of delivery, the potential side effects, the measurement of success and the plans for the end of the trial. You must be fully informed in order to make the right decision for your personal circumstances.
Be realistic about the chances of success and accept that your perception as a patient may well be different from that of the scientific community. Be prepared to stand up for yourself and your beliefs, be an integral part of the team and never forget that you are the essential element with a valid opinion.
Participating in the trial has given me new belief in myself and what I am capable of, as well as providing hope for the thousands of people also afflicted. I have contributed, and continue to contribute, to the future of research into Parkinson’s and that gives me tremendous pleasure and a feeling of worth.
Parkinson’s research studies are looking for participants right now. Studies range from simple questionnaires you can complete at home to trials testing experimental treatments. And it’s not just people with the condition that can take part, people without Parkinson’s are needed too.
Find out what’s happening near you by browsing our Take Part Hub.