From 2013-17 a group of 42 people with Parkinson’s were recruited on to an innovative & ground breaking clinical trial in Bristol, England.
The GDNF trial showed remarkable improvements in participants’ brain scans, but failed to meet the required end points and the trial ceased.
The GDNF Participant Group was formed when the trial ended – the volunteers from the trial were determined that the efficacy of GDNF should be further investigated and given another opportunity based on their personal experiences of improved symptoms.
This website charts the GDNF Participants’ Journey through the years since and their determination to have this particular Neurotrophic factor revisited scientifically.
We are now raising awareness and funds for further investigation into GDNF and other neurotrophic factors, that are also showing real promise.
We invite you to explore our website, read our stories, and form your own opinion.
Scroll down for "Patient Advocacy" and "What is GDNF?"
Patient Advocacy
We will be sending four Working Party members to the World Parkinson's Conference being held in Barcelona from 4th to 7th July, 2023. This will be an ideal opportunity to network with delegates from around the world and raise the profile of GDNF. We are extremely grateful to Funding Neuro, Parkinson's UK and Cure Parkinsons for their sponsorship.
Neurotrophic Factors Update by Dr Alan Whone
Dr Alan Whone, Principal Investigator, focuses on the clinical trial which ended in 2019 and used the neurotrophic factor GDNF to try to restore the brain of people with Parkinson’s.
He also talks about growth factors of other types and other means of delivering these to the brain including viral therapy.
His presentation is a reflection on what has been learnt from the trial and how this knowledge has to be factored in and considered in future trials, particularly the participant experience. Also included is a summary of what has been learnt from further analyses of the past trial data, and how the information can be applied to optimise the success of future trials.
Dr Alan Whone continues to work closely with Krystof Bankiewicz who has 5 years of data which supports the safety of treatment with GDNF from the Phase 1 Interventional MRI - guided Putaminal Delivery of AAV 2 - GDNF Gene Therapy clinical trial with the intention of bringing this procedure to the UK.
GDNF Working Party
Strategic Plan for The GDNF Participant Group’s Campaign to end Parkinson’s. The Working Group represents the interests of the participants and consists of 5 participants, 1 participant's carer and one person with Parkinsons' who did not participate in the trial.
Our Vision:
Ending Parkinson’s
Our mission:
To build a sense of urgency to end Parkinson’s by uniting science and People Living with Parkinson’s in an atmosphere of collaboration and mutual respect.
Aims:
- To raise global awareness and a belief in the progress being made in proving neurotrophic factors to be a potential disease modifying treatment.
- To raise funds internationally to support research into Neurotrophic Factors.
- To recognise that quality of life matters by having a properly funded and approved trial within twelve months and to ensure that PLWP are an integral part of all future trial design as equal partners, and that lessons are learnt from previous trials.
GDNF IAB
Following Parkinson's UK's successful acquisition of the licence for GDNF, a new trial is currently being investigated. The Involvement Advisory Board (IAB), exists to ensure that the needs and welfare of PLWPs are incorporated into the trial design. Membership includes three representatives from the GDNF Participant Group.
Mission statement
To provide strategic oversight of involvement to ensure the views, experiences and needs of people with Parkinson's are integrated in the development of a new trial for GDNF.
This will include:
- Identifying when and where involvement will have the greatest impact
- Planning high quality and meaningful involvement activities and evaluating the impact of involvement throughout the project
Vision
To pioneer an innovative approach for patient and public involvement and share our learnings to improve involvement in clinical trial design for future clinical trials.
Would you like to learn more about the GDNF Bristol trial from a participant?
We have presented details of the trial at many locations around the UK, mainly to Parkinsons UK branches. Please contact us if you would like a participant to talk to your group, either in person or virtually. We make no charge for this, but would appreciate travelling expenses to be reimbursed.
Please click on this link to find interesting articles, books and videos relating to GDNF.
Become a PD Avenger
We are a global alliance of people with Parkinson’s, our partners and friends, standing together demanding change in how the disease is seen and treated.
We add urgency to research, wellness and advocacy by uniting people and organizations to the cause of ending Parkinson’s.
Ongoing projects
Both of the studies below were developed in the aftermath of the GDNF trial after representations by the GDNF Participants Group. Our aim is to ensure that future participants of clinical trials had a better experience and to ensure that assessment tools in future trials were fit for purpose.
The group played a major role in not only the design of these projects, particularly LEARN, but also provided the majority of the participants for both. Our members also appear in the finished videos for the LEARN study.
LEARN
Listening to the experience of participants in neurosurgical trials.
This project was supported by the GDNF Participant group who advised on content and question structure. The GDNF participants formed a large proportion of the respondents who were interviewed in order to capture their views and comments on the trial. Family members also contributed to this extensive study which has captured the experience of taking part in a clinical trial and resulted in the production of videos aimed at future volunteers.
The LEARN study resourcing tools will be launched at the World Parkinsons Conference in July 2023, after which we will update this section
Further information can be found at: https://www.cardiff.ac.uk/centre-for-trials-research/research/studies-and-trials/view/learn
University of Bristol PD Sensors (SPHERE)
The vision of SPHERE is to impact a range of healthcare needs by monitoring patients in their home environment using sensors and digital technology. Since its inception the project has been working with end users and the public to develop a multi-sensor fusion approach to sensing of health-related behaviours such as sleep, physical activity, eating, domestic chores and social contact. The project has developed custom worn and non-worn sensors, video sensors, low power connectivity solutions and machine learning to reason from these data streams.
Our aim is to ensure that the tools used for assessing improvements in symptoms are fit for purpose and digital wearables and sensors are one way of achieving this. The GDNF Participants have supported this project by staying in a week in the SPHERE house in Bristol which has been equipped with multiple sensors in most rooms. Movement and sleep were recorded and assessed by continuously monitoring volunteers as part of the PD Sensors trial. Please keep an eye on this page for news and more information.
Further information can be found at: https://www.bristol.ac.uk/engineering/research/digital-health/research/sphere/
Scroll down for "What is GDNF?" and "The Parkinson’s Drug Trial: A Miracle Cure?"
So what exactly is GDNF?
At present only treatments that relieve the symptoms of Parkinson’s are available. What is needed is a treatment which slows or, even better, reverses disease progression. Glial cell line-derived neurotrophic factor (GDNF) may be such a treatment.
GDNF is a naturally occurring protein that, when applied directly to parts of the brain damaged by PD may produce re-growth of damaged brain cells and so reverse PD.
Like many other medicines, GDNF cannot reach the brain if given by mouth or by injection into a vein. This is because a natural shield the “blood brain barrier” prevents GDNF from leaving the bloodstream and getting into the brain. That is why, in order to get it to damaged cells in the brain it must be given directly into the brain through tiny implanted plastic tubes which connect to a port behind the ear.
Previous trials
GDNF has previously been given directly into the brain in animal studies and PD patient trials. Two early small trials with 15 PCD patients in total showed that continuously dripping GDNF into the brain down small tubes reduced PD symptoms. Brain scans suggested that this improvement was because GDNF had repaired damaged dopamine brain cells. However, a separate larger trial of over 30 patients did not show improvement in PD symptoms even though improvements in brain scans in those receiving GDNF were seen. This larger trial stopped early because a study in monkeys being performed at the same time raised questions over safety, since that time further patient trials have not been performed.
Reviewing all the studies suggests that the failure to improve symptoms in the larger trial may have been due to the way GDNF was delivered into the brain. The safety issues in 4 out of over 70 monkeys investigated may have been related to the very high dose of GDNF administered and no previous human subjects, from the previous studies mentioned above, developed cerebellum type brain problems. The delivery system developed for this placebo-controlled trial should allow GDNF to be given more reliably into parts of the brain damaged by PD.
Interestingly, participants in the larger human trial were so confident of the efficacy of GDNF that they unsuccessfully sued the organising company in an attempt to have the trial reinstated.
The Bristol Phase 2 GDNF trial, 2013 to 2017
Funding
The trial was funded jointly by Parkinson’s UK, Cure Parkinson’s and Funding Neuro.
Eligibility criteria
Patients who were considered likely to meet certain suitability criteria for this trial and who provided fully informed consent to participate had screening blood tests and clinical assessments. As part of this we were asked to stop PD medication overnight to allow assessment of the severity of symptoms.
Surgery
A three hour MRI scan was performed under general anaesthetic to plan the surgery which was carried out by a robot under close supervision. During the surgery 4 tiny plastic infusion tubes were inserted into the putamen area of the brain. Two on either side of the brain. These tubes connect to a single metal port that can be accessed as needed from the outside.
Infusions
Patients were randomly allocated to either the placebo or GDNF group. Those not in the GDNF group would receive a placebo instead of GDNF for the first nine months of the trial. Infusions took place every four weeks at which time a tube was connected to the port on the side of the head. Neither the patient nor the research team knew who was receiving placebo.
Scans
In addition to the initial MRI scan, several further scans were carried out during the trial. These were to check that the port and tube system were working well enough to allow infusion . Every patient also had a PET scan at the beginning of the trial and again after nine months.
Off assessments
Every eight weeks participants were required to stop all medication and undergo video recorded assessments. Once these were complete, a full dose of medication was administered and once this had taken effect, all tests were repeated.
Results
When the results were announced in a conference call with all participants on 7th July 2017, there was a hushed silence when the time came to relay the result, champagne corks were ready to pop and parties due to break out around the country. We knew that GDNF worked, now all we needed was the go-ahead to continue infusions. But this was not to be the celebration we had all planned.
To the surprise of both those assembled around the conference table and those on the conference call, GDNF had not reached the primary end point. This is a target that is set during the trial design.
Subsequent analysis of the statistics indicates that had a different primary end-point been chosen, then the result could have been so different.
Scroll down for "The Parkinson’s Drug Trial: A Miracle Cure?" and "Interesting Watches"
The Parkinson’s Drug Trial: A Miracle Cure?
Filmed over six years, 42 people with Parkinson’s take part in a groundbreaking medical trial. Can the results give hope to 10 million Parkinson’s sufferers worldwide?
This is our story, hopefully you’ve seen it, it's not currently online but we are hopeful for future availability.
We found the results truly life changing.
The trailer for the program is opposite. Hopefully it will help you understand why we’re so excited, why we’re working so hard, why we’re willing to push so far to get this drug and delivery system back into a treatment and even a cure for Parkinson’s.
Scroll down for "Interesting Watches" and "Darren Calders story"
Interesting Watches
Florence Pite Lecture 2018
Lesley Gosden's talk which starts at 6mins 50 seconds and ends on 20mins can be found by clicking this link.
Patients as Partners 2020 Keynote speaker
Lesley Gosden opens the 2020 Patients as Partners conference.
Scroll down for "Darren's story" and "Help Us Find a Cure"
I am Darren Calder and I have Parkinson’s.
Diagnosed back in 2005, they say life begins at 40…. it was certainly the start of a whole new meaning of life for me.
In 2013 I took hold of the reins to guide my destiny and became a participant of a drug trial, documented on the BBC 2 show ‘The Parkinson’s Drug Trial: A Miracle Cure?’
GDNF is a protein which was under clinical trial for the treatment of Parkinson’s. Following the ground-breaking Phase 2 trial, I am raising funds for further investigation into this promising treatment which could lead to the next Phase trial.
I have developed this website to help keep the GDNF story alive because I have complete belief in its efficacy, to convey the importance of taking part in clinical drugs trials and to raise the profiles of those incredible people who are proud to say we are “The GDNF Believers”.
Scroll down for "Help Us Find a Cure" and "Latest News"
Help us reach our goal, help us find a cure.
We are holding events throughout the year to reach a combined target of £1 Million, raised by the participants of the Phase 2 study. There are three charities actively involved whose work stands out and our aim is to support their efforts by raising the profile of neurotrophic factors, and fundraising on their behalf.
Cure Parkinson’s (CP) has one goal – to cure Parkinson’s. CP funds innovative and promising research which is dedicated to finding new treatments that can slow, stop or reverse Parkinson’s.
New technology that we support allows drugs to get to where they need to be in the brain. With it we are able to bring hope for the first time to sufferers of serious conditions like Parkinson’s or brain tumours. With your help we can pioneer new treatments and accelerate cures.
We are Parkinson’s UK. Powered by people. Funded by you. Improving life for everyone affected by Parkinson’s. Together we’ll find a cure.
Scroll down for "Latest News"
Latest News
A new book by Andy Rollin
Andy will answer the question “What happened next?” later this year when his latest book is published, he continues the tale of his involvement with all things GDNF, the GDNFer’s and his personal Parkinson’s highs and lows.
GDNF! What Happened To Me by Andy Rollin
Andy was diagnosed with Parkinson’s at the age of 47, but surely that is something that old people get? 5 years later he had a once in a lifetime chance to participate in ground breaking clinical trial to see if something called GDNF could slow, stop or reverse his Parkinson’s.
Ending Parkinson’s Disease Book
A Prescription for Action by Ray Dorsey, Todd Sherer, Michael S. Okun, Bastiaan Bloem. The authors of this book have proposed a bold PACT to Prevent the disease, Advocate for Policies, Care for Patients and Treat the condition.