Results from a pioneering clinical trials programme that delivered an experimental treatment directly to the brain offer hope it may be possible to restore the cells damaged in Parkinson’s disease.

The Journal of Clinical Studies reports a large team of researchers from various institutions across the UK and Canada, including the University of Bristol, Cardiff University and the University of British Columbia, conducted the trial.

In the study, the researchers aimed to restore degrading dopamine producing brain cells in people who doctors had diagnosed with Parkinson’s disease. As dopamine is a neurotransmitter that helps regulate the control and agility of body movements, the impaired production of dopamine, due to changes in the brain cells that release it, leads to the motor symptoms that characterise Parkinson’s disease. The research team conducting the current trial decided to try and rehabilitate those brain cells by upping the levels of glial cell line derived neurotrophic factor (GDNF), a type of protein that supports neuronal health.

Initially, the research team conducted a small pilot study with six participants, all living with Parkinson’s disease, their main goal being to establish whether or not the new therapeutic approach was safe. The next stage saw thirty five more participants with Parkinson’s disease take part in a double blind trial which lasted forty weeks. Finally, the researchers organised an open label trial, building on the results of the previous tests. In this trial, volunteers who had previously received GDNF continued to have this treatment for another forty weeks, while those who previously received a placebo now had GDNF for forty weeks. The researchers write “From October 2013 through to April 2016, all 41 patients completing the parent study were screened for participation in the extension trial.”

To receive the drug, the participants agreed to have a special port implanted into their skills, which allowed the drug infusions to reach their brains directly. Following implantation, the volunteers received, on the whole, over one thousand drug infusions once every four weeks.

When they analysed the results of the first forty week trial, the researchers saw no changes in the brains of participants who had received a placebo. However, they noted volunteers who received the GDNF treatment had a 100% improvement in the putamen, the brain region which contains dopamine producing cells.

At the eighteen month mark, when participants had been on the GDNF treatment for either nine months or the full eighteen months, the researchers found everyone had begun experiencing moderate to significant improvements of their motor symptoms when they compared them with their performance scores before the trials. The researchers also concluded prolonged exposure to GDNF was safe.

Bristol University reports Dr Alan Whone, Principal Investigator on the GDNF trial and Consultant Senior Lecturer in Movement Disorder at the Bristol Medical School: (THS), 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.”

Dr Arthur Roach, Director of Research at Parkinson’s UK, said “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.”

Professor Steven Gill, lead neurosurgeon and designer of the device and Honorary Professor in Neurosurgery at the Bristol Medical School, said “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.”

Helen Matthews, Deputy CEO at The Cure Parkinson’s Trust, said “It is fantastic to see these encouraging results. This was an extremely complex trial delivered with thanks to the dedication of the entire trial team of participants, researchers, industry and charities. The Cure Parkinson’s Trust has been involved in and has championed the GDNF story since 2003 through the commitment and determination of the charity’s late co-founder and president Tom Isaacs. These results, particularly the brain scans show that GDNF, delivered with Convection Enhanced Delivery, has promise as a potential treatment to slow, stop or even reverse Parkinson’s. However, it is critical we now concentrate on how to best support moving GDNF forward, to understand if it can be a viable treatment to potentially regenerate dopamine cells and impact the lives of people living with Parkinson’s.”

Dr Erich Mohr, Chairman and CEO of MedGenesis, the biotechnology company who owns GDNF, said “While the results are not as clear cut as would have been desirable, when you look more closely there are exciting signs of promise for Parkinson’s. In particular, when the scores on three of the key assessments are combined – motor response, activities of daily living and good quality “on time” – it reveals a highly significant difference between the treatment and placebo groups. We believe this experimental combined score, which we call the Parkinson’s Disease Composite Score (PDCOMS), may better capture the full effects of GDNF and we’re working to get it scientifically validated so that it can be used in future trials.”

Paul Skinner, General Manager for Neurological Products at Renishaw, the engineering company which developed and built the device, said “It has been a privilege to work alongside the study team and with the participants in this ambitious trial. We are very encouraged that there were changes in the brain scans, demonstrating that GDNF is having an effect, and that the delivery system achieved precision administration of drugs into the brain. This provides great potential for using the drug delivery system, being developed by Renishaw, for future Parkinson’s studies and experimental treatments for other neurodegenerative diseases and brain tumours.”

The study is published in the Journal of Parkinson’s Disease.