Engineered solution delivers key protein to brains of Parkinson’s trial patients

The study, funded by Parkinson's UK with support from The Cure Parkinson's Trust and in association with the North Bristol NHS Trust and Bristol University, wanted to see if increased levels of GDNF (Glial Cell Line Derived Neurotrophic Factor, a naturally-occurring protein) can regenerate dying brain cells in people with Parkinson’s and reverse their condition.

To get GDNF to the brain cells that need it, a specially designed delivery system was developed. A total of 41 participants underwent robot-assisted surgery to have four tubes placed into their brains, which allowed GDNF to be infused directly to the affected brain areas via a port in the side of their head.

Six 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 placebo infusions. After the initial nine months all participants had the opportunity to receive GDNF for a further nine months.

While there were signs of improvements in those receiving GDNF, there was no significant difference between the active treatment group and those who received placebo on any assessments of Parkinson's symptoms. Results from brain scans, however, revealed promising effects of GDNF on damaged brain cells.

According to Bristol University, 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, but the group that received GDNF showed a 100 per cent improvement in a key area of the brain affected by the condition.

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.”

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, but these improvements need to be treated with caution because everyone knew they were receiving the active treatment and there was no comparison group.

Prof Steven Gill, lead neurosurgeon and designer of the delivery system and Honorary Professor in Neurosurgery at the Bristol Medical School: (THS), 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.”

Paul Skinner, general manager for Neurological Products at Renishaw, which developed and built the device, said: "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 findings from these ground-breaking trials are published in Brain and the Journal of Parkinson's Disease. The trial also features in an upcoming two-part documentary series for BBC Two – The Parkinson's Drug Trial: A Miracle Cure?

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