GDNF Trial Results

GDNF Trial Results

Posted on 27th February 2019

Pioneering trial for Parkinson’s Disease… GDNF the results are out!

Funding Neuro | parkinson's disease

The results have been published for this ground-breaking trial, aimed to investigate whether boosting the levels of a naturally-occurring protein, Glial Cell Line Derived Neurotrophic Factor (GDNF), can regenerate dying neurons in the brain and reverse the condition.  This has never been achieved previously.

 The trial involved the delivery of GDNF directly into the brain using Renishaw’s specially designed convection enhanced delivery system, invented by Professor Steven Gill. The trial was funded by Parkinson’s UK with support from Cure Parkinson’s Trust and seed funding from Funding Neuro, in association with the North Bristol NHS Trust. 

Participants underwent robot-assisted surgery where four tubes were inserted into their brains, to infuse the GDNF directly and with precision accuracy into the putamen, the area of the brain which is affected in Parkinson’s Disease.

Six people took part in the initial pilot study to assess the safety of the treatment approach. A further 35 people then participated in the nine-month double blind trial, where half were randomly assigned to receive monthly infusions of GDNF and the other half were given placebo infusions. After the initial nine months on GDNF or placebo, all participants then had the opportunity to receive GDNF for a further nine months.

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

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

All participants had brain scans before starting the trial and after nine months to assess how well their dopamine-producing brain cells were working. After nine months, there was no change in the scans of those who received placebo, whereas the group who received GDNF showed an improvement of 100% in the putamen, 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. 

Dr Alan Whone, Principal Investigator on the GDNF trial, said: “The spatial and relative magnitude of the improvement in the brain scans is beyond anything seen previously in trials of surgically delivered growth-factor treatments for Parkinson’s. This represents some of the most compelling evidence yet that we may have a means to possibly reawaken and restore the dopamine brain cells that are gradually destroyed in Parkinson’s. Its failure to produce the same effect on symptoms could be for a number of reasons. It may be that the effects on symptoms lag behind the improvement in the brain scans, so a longer double-blind trial may have produced a clearer effect.

It’s also possible that a higher dose of GDNF would have been more effective, or that participants at an earlier stage of the condition would have responded better. This is why it’s essential to continue research exploring this treatment further – GDNF continues to hold potential to improve the lives of people with Parkinson’s.”


GDNF Trail Professor Steven Gill
Professor Steven Gill

Professor Steven Gill. Lead neurosurgeon and designer of the CED device, commented. “This trial has shown that we can safely and repeatedly infuse drugs directly into patient’s brains over months or years through a small implanted port that emerges through the skin behind the ear. This is a significant breakthrough in our ability to treat neurological conditions such as Parkinson’s because most drugs that might work cannot cross from the blood stream into the brain due to a natural protective barrier.  Even at a low dose we have seen evidence of patient improvement, which is incredibly encouraging. Now we need to move towards a definitive clinical trial using higher doses and this work urgently needs funding. I believe that this approach could be the first neuro-restorative treatment for people living with Parkinson’s which is of course, an extremely exciting prospect is.”


What’s next? 

The next and definitive step is for a further trial, which is required prior to approval of GDNF therapy.  This will include a dose escalation to see if they can increase the rate and magnitude of GDNF’s benefit. The team are now able to deliver at higher dose than was possible in this phase II trial. Experiments that were done in parallel with the trial have shown that doses 4 fold higher are safe. The trial will  also validate a potentially better way of evaluating disease severity in people living with Parkinson’s using a new scoring system. This quantifies how much of the day their Parkinson’s Disease is well controlled and what they are able to do in addition to measuring their motor function. The current standard only looks at the motor function off medication and does not reflect what matters to patients.

Since Pfizer dropped all their drug development programs for neurodegenerative diseases. With that GDNF for Parkinson’s, it has not been possible to find another large pharmaceutical company or investors to invest the $100 million plus required. That would take GDNF forward to market authorisation. This is despite the regulatory bodies, the EMA and the FDA  supporting a definitive phase III based on the phase II data. This may be because the mode of delivery is unfamiliar as it requires complex surgery, but also because they require confidence that a higher dose will increase the magnitude of benefit. 

GDNF is the only therapy which has been shown to restore the function of dying dopamine neurons in the brain of people living with Parkinson’s and with this there is reversal of symptoms. 

There are now major concerns that this neuro-restorative therapy. This holds up so much hope for those with Parkinson’s will be lost unless a small lead-in phase III study can be initiated. Within the next 6 months  and demonstrate the enhanced efficacy of this therapy at a higher dose. Investors have already indicated their willingness to invest the large sums. Which are necessary to take this through to market authorisation should such a study have a positive outcome. The cost of the lead-in study will be £4million.  Many of the trial participants are already fundraising for this. With Funding Neuro having a dedicated fund for this vital stage lead-in study.  

If you would like to help to further the research into GDNF for Parkinson’s, you can donate via our website using paypal or by clicking on the Just Giving link here and visiting our fundraising page! With your help, hopefully we will reverse Parkinson’s Disease!   

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