A new clinical trial of GDNF — an update
In February 2021, we announced our bold plans to invest in driving forward research into the experimental Parkinson’s treatment, GDNF. We created a dedicated company — Vivifi Biotech — to lay the groundwork for a new clinical trial. In this post, we’d like to update you on our progress with this important and challenging project.
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GDNF — which stands for Glial Cell-line Derived Neurotrophic Factor — is a protein that is naturally produced inside the brain with remarkable properties. In the lab, it’s been shown to help damaged brain cells to survive, recover and regrow — offering hope that boosting its levels in the right parts of the brain could provide similar benefits for Parkinson’s.
Over the past 20 years, there have been a number of attempts to deliver GDNF to the brain in people with Parkinson’s in clinical trials. To date, no trial has successfully proved that GDNF ‘works’ — ie can slow, stop or reverse the progression of Parkinson’s when compared to a placebo.
But despite these disappointments, brain scans and reports from participants have shown signs that GDNF does have the potential to be a transformative therapy. Read more about this in our previous blog.
Driven by this potential and the unwavering determination of the participants to prove that the benefits they felt from the treatment were not represented in the published results, Parkinson’s UK stepped forward with a bold plan. We would take on the challenge of planning a new trial to investigate GDNF’s ability to slow, stop or reverse Parkinson’s. Building on lessons learnt from previous studies, we would endeavour to develop a plan for a trial that could provide a definitive answer on what potential GDNF holds in Parkinson’s.
Putting together a new trial
To ensure a future trial has a genuine chance of success, we have been working hard to overcome a number of challenges over the past 12 months. And we’ve made significant progress.
The rights to GDNF
The first thing we needed to do to make a new trial possible was to gain ownership of the GDNF programme from the previous owners — a biotech company called MedGenesis.
This involved sorting out some complicated legal issues as well as securely transferring all the data associated with the previous studies.
Our new company — Vivifi Biotech — successfully acquired the rights and data in May 2021.
A new trial design
Perhaps the most crucial part of putting together a new clinical trial is designing a study that has the best chance of scientific success, is acceptable and attractive to people with Parkinson’s, and also meets the requirements of regulatory agencies.
To achieve this, we have been working intensively with independent experts, the team from the previous trial and people living with Parkinson’s. A dedicated GDNF Involvement Advisory Board has allowed participants from the previous trial to feed into key aspects of the study design — including dose, trial length, support needs and how to measure success.
Together, we are designing a study that is scientifically strong and takes into account the needs and experiences of people with the condition.
As a result, we have now reached the important stage of sharing the proposed trial with regulatory agencies for their feedback. The first of these meetings was encouraging and we are aiming to have further discussions in the coming months.
A supply of GDNF
Unlike manufacturing most drugs, which are relatively simple chemical structures, GDNF is a protein and is much more complicated to make. It has to be made by the bacteria E. coli and only a small number of manufacturers can do this.
We are currently reviewing options for drug manufacturers. We are confident that we will be able to find a suitable supplier.
A way to deliver GDNF
Another challenge that comes with GDNF being a large protein is that it cannot reach the brain when it’s given in a pill or even as an injection into the bloodstream. It needs to be delivered directly using a specially designed device that is implanted in the brain.
There are only a small number of companies with the specialist engineering skills needed to develop and deliver such devices for a clinical trial as ambitious as GDNF. We are currently reviewing options for possible device suppliers and discussing terms. We are hopeful of securing an appropriate supplier but this remains a significant challenge.
Investors to help fund the trial
The final piece we need to make a new clinical trial is the funding. From the outset of this project, we have always been clear that a new GDNF trial is not something that Parkinson’s UK can fund alone.
We need to attract external investment to meet the significant price tag of a new study which is likely to be in the region of £10–15million. We’re also keen to attract investment from partners with experience and a track record of developing complex new therapies who will bring expertise and know-how to the programme as well as funds.
Now that we have a solid scientific plan and have made sufficient progress with suppliers we are about to start reaching out to potential investment partners.
When will we know if a new trial can happen?
Despite many challenges over the past year, we have made very good progress.
There are no guarantees but we are hopeful that we will solve the remaining issues and be in a position to make a final decision on whether it is possible to move forward with a new trial before the end of 2022.
We will share the outcome with the Parkinson’s community as soon as we are able to.
