Results from a pioneering clinical trials program that delivered an experimental treatment directly to the brain may offer hope to restore damaged brain cells in Parkinson’s disease (PD).
The studies, which have been published in Brain and the Journal of Parkinson’s Disease, aimed to investigate whether boosting the levels of GDNF could regenerate dying brain cells in individuals with PD and reverse their condition.
A specially designed system was developed in order to get GDNF to the brain cells that require 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.
The initial pilot studied involved six participants and assessed the safety of the treatment approach. A further 35 people then participated in the 9-month, double-blind trial where half were randomly assigned to receive monthly infusion of GDNF or placebo. After the initial 9 months on GDNF or placebo, all study participants were given the opportunity to receive GDNF for a further 9 months.
During this time, the researchers reported some encouraging signs of improvement in those receiving GDNF, however, there was no significant difference between the treatment group and those receiving placebo on any assessments of Parkinson’s system.
Results from the brain scans, on the other hand, revealed extremely promising effects on damaged brain cells. All participants had brain scans prior to starting the trial and after 9 months to assess how well their dopamine-producing brain cells were working.
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After 9 months, it was revealed that there was no change in the scans of those who received placebo, whereas the group receiving GDNF showed an improvement of 100% 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, when all participants had received GDNF, it was reported that both groups demonstrated moderate-to-large improvements in symptoms compared to their scores before they started the study. Although this offers encouragement that the treatment may have long-term beneficial effects, these improvements need to be treated with caution as the study participants knew they were receiving the active treatment.
Alan Whone, Principal Investigator of the trial, commented: “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.”
Whone concluded: “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.”
Sources: Whone A, Luz M, Boca M et al. Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson’s disease. Brain 142(3), 512–525 (2019); Whone AL, Boca M, Luz M et al. Extended treatment with glial cell line-derived neurotrophic factor in Parkinson’s disease. J. Parkinson Dis. doi:10.3233/JPD-191576 (2019) (Epub ahead of print); https://eurekalert.org/pub_releases/2019-02/pu-pto022519.php