A series of clinical trials have tested an experimental treatment for Parkinson's disease that uses a novel approach: administering the drug straight into the brain via implanted ports. The leading researchers believe this may be a "breakthrough" therapeutic strategy for neurological conditions.

In a new series of studies that culminated with an open-label trial (where participants were aware of what treatment they would receive), scientists have begun testing the effectiveness of a new treatment—and method of delivery—or Parkinson's disease.

A large team of researchers from various institutions across the United Kingdom and Canada, including the University of Bristol and Cardiff University in the UK and the University of British Columbia in Vancouver, Canada, devised and conducted the trial. In the study, the researchers aimed to restore degrading dopamine-producing brain cells in people whom doctors had diagnosed with Parkinson's disease.

Since 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 characterize 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.

In the study paper reporting the results—which appears in the Journal of Parkinson's Disease—the scientists explain that not only did they test a novel therapy but also an innovative administration method—through a port they implanted in the skull.

Very encouraging results

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 35 more participants with Parkinson's disease take part in a double-blind trial where neither they nor the researchers administering the therapy knew whether each was dealing with the experimental treatment or a placebo.

This trial lasted for 9 months (40 weeks), during which the team gave half the volunteers monthly infusions of GDNF and administered a placebo to the other half who acted as the control cohort. Finally, the researchers organized 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 40 weeks.

At the same time, those who previously received a placebo now had GDNF for 40 weeks. "From October 2013 through to April 2016, all 41 patients completing the parent study were screened for participation in the extension trial," the researchers write. To receive the drug, the participants agreed to have a special port implanted into their skulls, which allowed the drug infusions to reach their brains directly. Following implantation, the volunteers received infusions once every 4 weeks, for a total of over 1,000 drug infusions.

When they analyzed the results of the first 9-month (40-week) trial, the researchers saw no changes in the brains of participants who had received a placebo. However, they noted that volunteers who had received the GDNF treatment had a 100% improvement in the putamen, the brain region which contains dopamine-producing cells.

"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," points out the study's principal investigator Alan Whone.

"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," Whone goes on to argue.

'A significant breakthrough'

At the 18-month mark, when participants had been on the GDNF treatment for either 9 months or the full 18 months, the researchers found that everyone had begun experiencing moderate to significant improvements of their motor symptoms when compared with their performance scores before the trials. The researchers also concluded that prolonged exposure to GDNF was safe.

However, the team warns that at the end of the open-label trial, there were no significant differences in terms of symptom improvement between the participants who had received GDNF for 40 weeks (9 months) and those who had received it for double that time period. For this reason, the researchers argue that they need to do further studies to assess how long a person should receive the treatment to reap the most benefit.

Nevertheless, Steven Gill, study co-author and designer of the innovative drug-administration device, stresses that the current findings suggest that this new therapy is absolutely safe and feasible, and people can administer it for a long time.

Moreover, he notes that administering drugs directly into brain areas they target has the potential to revolutionize therapeutic approaches to neurological conditions. "This trial has shown that we can safely and repeatedly infuse drugs directly into patients' brains over months or years," Gill says.

"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."

—Steven Gill