GDNF clinical trial offers hope for restoring brain cells damaged in Parkinson’s

The pioneering GDNF clinical trials programme delivered an experimental treatment directly to the brain. The trial results offer hope that it may be possible to restore the cells damaged in Parkinson’s.

The multimillion-pound study aimed to investigate whether boosting levels of GDNF, a naturally-occurring protein, can regenerate dying brain cells in people with Parkinson's. This would ultimately reverse the condition – something that no existing treatment can do.

The study was funded by Parkinson's UK with support from The Cure Parkinson's Trust and in association with the North Bristol NHS Trust.

A groundbreaking clinical trial

To get GDNF to the brain cells that need it, a specially designed delivery system was developed. The participants underwent robot-assisted surgery to have 4 tubes carefully placed into their brains. This allowed GDNF to be infused directly to the affected brain areas with pinpoint accuracy, via a port in the side of their head. 

In total, 41 participants took part in the double-blind trial, where half were randomly assigned to receive monthly infusions of GDNF and the other half placebo infusions. 

After the initial 9 months on GDNF or placebo, all participants had the opportunity to receive GDNF for a further 9 months.

Promising trial results

While there were some encouraging signs of improvements in those receiving GDNF, disappointingly there was no significant difference between the active treatment group and those who received placebo on any assessments of Parkinson's symptoms.

However, results from brain scans revealed extremely promising effects on damaged brain cells.

All participants had brain scans before starting the trial and after 9 months to assess how well their dopamine-producing brain cells were working.

After 9 months, there was no change in the scans of those who received placebo. But the group who received GDNF showed an improvement of 100% in a key area of the brain affected in the condition – offering hope that the treatment was starting to reawaken and restore damaged brain cells.
By 18 months, when all participants had received GDNF, both groups showed moderate to large improvements in symptoms compared to their scores before they started the study.

This offers further encouragement that the treatment may have long-term beneficial effects. But because everyone knew they were receiving the active treatment and there was no comparison group, these improvements need to be treated with caution.

Hope for future clinical trials

Dr Arthur Roach, Director of Research at Parkinson's UK, says:

"While the results are not clear-cut, the study has still been a resounding success. It has advanced our understanding of the potential effects of GDNF on damaged brain cells, shown that delivering a therapy in this way is feasible and that it is possible to deliver drugs with precision to the brain.

"All the partners involved – including the scientific team, companies, charities and patients – are continuing to work together to explore possible routes to further studies. It is vital that we learn everything we can from these recent trials and we're keen to work with both the wider research community and people affected by Parkinson's so that any future trials have the very best chance of success."

A positive experience

Trial participant Tom Phipps, 63, from Bristol, was the first person to undergo the pioneering surgery. He says: 

"Clinical trials around Parkinson's are so important because it's a condition that's not going to go away unless people do proper research. Being a scientist myself – I'm a graduate of biological sciences – I wanted to contribute. 

"During the trial I noticed an improvement in my mobility and energy levels, and I was even able to reduce my medication. Since it ended, I have slowly increased my medication but I still ride my bike, dig my allotment and chair the local branch of Parkinson's UK. 

"My outcome was as positive as I could have wished for, I feel the trial brought me some time and has delayed the progress of my condition."

Tom Phipps, GDNF trial participant

"The best part was absolutely being part of a group of people who've got a similar goal – not only the team of consultants and nurses, but also the participants.

"You can't have expectations – you can only have hope." 

Read more about GDNF

The trial has advanced our understanding of the potential effects of GDNF on damaged brain cells.

But there are still important questions to answer about GDNF's potential to be a life-changing treatment for people with Parkinson's.

Read more about GDNF, the results of the trial and what's next.