Washington: A pioneering clinical trial programme that delivered an experimental treatment directly to the brain, offers hope that it may be possible to restore the cells damaged in Parkinson’s.
The study, funded by Parkinson’s UK with support from The Cure Parkinson’s Trust and in association with the North Bristol NHS Trust, aimed to investigate whether boosting the levels of a naturally-occurring protein, Glial Cell Line-Derived Neurotrophic Factor (GDNF), can regenerate dying brain cells in people with Parkinson’s and reverse their condition.
This is something which no existing treatment can do.
A specially designed delivery system was designed to get GDNF to the brain cells that need it. In total, 41 participants underwent robot-assisted surgery to have four tubes carefully placed into their brains, which allowed GDNF to be infused directly to the affected brain areas with pinpoint accuracy, 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 than 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 on GDNF or placebo, all participants had the opportunity to receive GDNF for a further nine months.
While there were some encouraging signs of improvements in those receiving GDNF, disappointingly there was no significant difference between the active treatment group and those who received placebo on any assessments of Parkinson’s symptoms.
However, results from brain scans revealed extremely promising effects on damaged brain cells.
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 percent in a key area of the brain affected in the condition – offering hope that the treatment was starting to reawaken and restore damaged brain cells.
By 18 months, 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 but because everyone knew they were receiving the active treatment and there was no comparison group, these improvements need to be treated with caution.
The findings from the trials are published in Brain and the Journal of Parkinson’s Disease.
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,” adding, “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.’
The researchers further added that it is 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.
Dr. Arthur Roach, the study author, 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 therapy in this way is feasible and that it is possible to deliver drugs with precision to the brain.”
Professor Steven Gill, lead neurosurgeon, and designer of the 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 bloodstream into the brain due to a natural protective barrier.”
Helen Matthews, Deputy CEO at The Cure Parkinson’s Trust, said the results are encouraging, adding, “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, commented that while the results are not as clear cut as would have been desirable, they are exciting signs of promise for Parkinson’s. He added that, in particular, when the scores on three of the key assessments are combined – motor response, activities of daily living and good quality it reveals a highly significant difference between the treatment and placebo groups.