A study was conducted by the North Bristol NHS Trust and Bristol University 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. Their engineered solution that delivers a therapeutic protein to participants’ brains was a stride in the right direction, bringing them closer to a good treatment for Parkinson’s disease. This successful study was possible thanks to funding by Parkinson’s UK with support from The Cure Parkinson’s Trust.
The findings from these trials are published in Brain and the Journal of Parkinson’s Disease. The trial is also featured in a two-part documentary series for BBC Two—The Parkinson’s Drug Trial: A Miracle Cure?
The Study
The researchers had to develop a specially designed delivery system to get GDNF to the brain cells that need it. Robot-assisted surgery was carried out on 41 participants to have four tubes placed into their brains. These tubes allowed GDNF to be infused directly into the affected brain areas via a port in the side of their head.
First, there was an initial pilot study to assess the safety of the treatment approach. Six of the participants were a part of this phase. Next, there was a nine-month double-blind trial, where half were randomly assigned to receive monthly infusions of GDNF and the other half placebo infusions. The rest of the 35 participants were involved in this second phase. After the first nine months, all participants had the opportunity to receive GDNF for a further nine months.
The Results
There were signs of improvements in those receiving GDNF; however, there was no significant difference between the active treatment group and those who received placebo on any assessments of Parkinson’s symptoms. Nevertheless, the results from brain scans did reveal promising effects of GDNF 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. There was no change in the scans after the nine months for those who received a placebo, but the group that received GDNF showed a 100 percent improvement in a key area of the brain affected by the condition.
Dr. Alan Whone, principal investigator on the GDNF trial and senior consultant lecturer in movement disorder at the Bristol Medical School, Translational Health Sciences, 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.”
For the second round of 9 months, there was no placebo group; all participants received GDNF. By 18 months, both groups showed moderate to large improvements in symptoms compared to their scores before they started the study. Although, these improvements need to be treated with caution because everyone knew they were receiving the active treatment and there was no comparison group.
Conclusion
Prof Steven Gill, lead neurosurgeon and designer of the delivery system and Honorary Professor in Neurosurgery at the Bristol Medical School, Translational Health Sciences, 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 tumors.”
A newer strategy now being tested in China uses DREADDs chemogenetic therapy to suppress Parkinson’s circuits with an AAV-delivered designer receptor, offering a reversible, drug-controlled alternative to implanted hardware.
