GDNF — one year on

27 February 2020 marks one year since the results of a groundbreaking trial to test whether GDNF can slow, stop or reverse the progression of Parkinson’s were announced to the world. The trial was designed and managed by leading experts in the UK with international collaboration. Under the pioneering guidance of medical experts, 41 people with Parkinson’s helped test an experimental drug and revolutionary device to deliver it to brain cells with pinpoint precision. The results revealed promising signs of GDNF’s potential. Brain scans suggested that damaged cells were rekindled and participants reported significant and sustained improvements in their symptoms. But sadly, the crucial scientific assessments fell short of conclusively proving that GDNF was better than a placebo. If you watched the BBC documentary — The Parkinson’s Drug Trial — A Miracle Cure? — which followed eight of the 41 trial participants as they and their loved ones went on this journey, you may also have been left mystified by the disconnect between the scientific and personal conclusions. This is not the first time that this pioneering treatment has fallen at this hurdle. A previous phase 2 clinical trial conducted in the US also failed to demonstrate the effectiveness of the therapy, although many participants experienced significant benefits. These failures have been devastating for the participants. From their perspective, they experienced the benefits of an experimental treatment, only for the scientific results to snatch it away. It’s difficult to imagine being in that position. In the past year, I’ve met many of these amazing people. They tell me they’re still experiencing the benefits of taking part in the trial and that they are taking less medication now than before they started the trial 7 years ago. The sense of disappointment and frustration that a truly life-changing treatment may be within our grasp but without a clear route forward, is hard to describe. They won’t give up and neither will Parkinson’s UK. We are a charity that exists to find a cure and better treatments for Parkinson’s, and we will leave no stone unturned until we reach our goal. In GDNF, we may already have a treatment that could change the outlook for the millions of people living with Parkinson’s globally, and the millions more who have this condition but are yet to be diagnosed. I believe that this story isn’t over yet. And for the past year we’ve been working alongside the participants, the scientists, companies, and other charities to find a route forward for GDNF. Since the second trial ended, we’ve been working together on how to make a further trial a success. Learning from both trials, and the experiences of the participant group has given us good information. This can be used to give us a much better chance of designing a successful further trial, and ultimately getting a solution for everyone with Parkinson’s. No trial is risk-free, and I genuinely believe the potential of GDNF needs to be further explored. We were the majority funder of the last trial and are under no illusions about the considerable cost of funding another trial. If the next attempt can be structured in the right way with a strong chance of success, we’re ready and willing to bring our funds to the table. It’s why we exist. Alongside the work that is being done to explore GDNF further our research team is also keeping a close eye on the development of other similar approaches globally. In January, investigators leading a similar trial testing the safety and effectiveness of a closely related drug — CDNF — in Sweden and Finland, reported that they had successfully completed their main study. I’m looking forward to seeing their initial results when they are released later this year. In 2019, researchers presented the results of a phase 1 clinical trial designed to test the safety and tolerability of a gene therapy approach to delivering GDNF in Parkinson’s. Their aim is to use genetically engineered viruses to insert the genes required for making GDNF into the DNA of targeted cells within the brain. These genetically reprogrammed cells will then start making and releasing GDNF, generating a steady ongoing supply of the protein. One of the biggest challenges we face in developing new therapies like GDNF is finding safe and practical ways to deliver them into the brain. At the moment, this means invasive surgery like the trial participants underwent 7 years ago. This is because these proteins are too large to cross the blood brain barrier. However, progress is being made in developing molecules that could have similar effects to GDNF but that are small enough to pass from the bloodstream into the brain. Earlier this month, results from research, supported by Parkinson’s UK, indicated that a small molecule called BT13 may show significant promise. The hope is that these could be developed into drugs that could be taken more easily — such as in a pill or a simple injection. And through our Parkinson’s Virtual Biotech we are investing in a range of other approaches that have the potential to slow, stop and reverse the condition. Every day researchers are making progress towards better treatments for Parkinson’s, including GDNF and related advances. With their help, and yours, we’re here to find a cure and we won’t stop until we do.