New Treatment May Have the Potential to Slow, Stop, or Reverse Parkinson Disease

Results from a February study of a revolutionary treatment suggest that it may be possible to slow, stop, or even reverse the progression of Parkinson disease, according to findings in the Journal of Parkinson’s Disease.

The 3-part, experimental study investigated whether using a novel delivery system to increase levels of glial cell line-derived neurotrophic factor (GDNF) can regenerate dying dopamine brain cells in patients with Parkinson disease and even reverse their condition. GDNF is a naturally occurring protein that promotes the survival of many types of neurons.

“I believe that this approach could be the first neuro-restorative treatment for people living with Parkinson's, which is, of course, an extremely exciting prospect,” Steven Gill, MB, MS, FRCS, who designed the infusion device used in the study, said in a statement.

Researchers used robot-assisted neurosurgery to implant a specially designed delivery system, termed Convection Enhanced Delivery (CED), which allowed high flow rate infusion to be administered to patients every 4 weeks. Patients underwent a procedure to have 4 tubes implanted within their brains. GDNF was directly infused to targeted locations via a skull-mounted transcutaneous port located behind the ear. Following implantation, the trial team administered a total of more than 1000 brain infusions throughout the study. Patients demonstrated a high compliance rate of 99.1% and confirmed clinical feasibility and tolerability toward the administration process for repeated brain infusions.

Initially, 6 patients enrolled in a pilot study which evaluated the safety of the treatment approach. After the pilot study, 35 additional individuals participated in a subsequent 9-month double-blind trial. Half of the participants were randomly assigned to receive monthly infusions of GDNF while the other half received placebos.

Positron emission tomography (PET) brain scans from the group who received GDNF showed an improvement of 100% in the targeted area of the brain affected by Parkinson disease, leading researchers to believe that the treatment may have the potential to reawaken or restore damaged brain cells. There was no change in PET brain scans among the group that received placebo. After the trial period, no improvements in symptoms were observed in either group.

"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," the study's principal investigator Alan L. Whone, PhD, FRCP, Translational Health Sciences, Bristol Medical School, University of Bristol, said in a statement. "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."

Following the 9-month treatment period, a third, open-label extension trial was performed to investigate the effects and safety of continued exposure to GDNF for an additional period of 40 weeks. The group of patients who were already receiving GDNF continued to be exposed to the growth factor. The group that was receiving placebo for the first 40 weeks was then given GDNF.

The study's primary endpoint was the percentage change in the OFF state Unified Parkinson’s Disease Rating Scale (UPDRS) motor score from baseline to the conclusion of the 80-week period between the group that consistently received GDNF and the group that received placebo and then GDNF.

Although symptoms in both groups were found to either moderately or significantly improve after 18 months, once all participants had received GDNF, no significant differences between the groups in the primary or supplementary endpoints were observed throughout the study. However GDNF treatment was attributed to a significant increase in dopamine uptake.

Safety was assessed according to occurrences of adverse events (AEs), presence of anti-GDNF antibodies, and routine laboratory testing . While all patients experienced at least 1 AE between week 40 to week 80, none led to the discontinuance of receiving study medication. Serious AEs were reported for a total of 8 patients but were determined to be unrelated to study medication. GDNF was determined to by safe when administered over an extended time period.

"This trial has shown that we can safely and repeatedly infuse drugs directly into patients’ brains over months or years. 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,” said researchers in a statement.

Researchers believe that further studies are required to determine whether GDNF can reverse, slow, or stop the progression of Parkinson disease. They recommend implementation of a larger scale study that would administer higher doses of GDNF.

The study’s lead author emphasized, "It's essential to continue research exploring this treatment further. GDNF continues to hold potential to improve the lives of people with Parkinson's.”

Reference

Whone AL, Boca M, Luz M, et al. Extended treatment with glial cell line-derived neurotrophic factor in Parkinson’s disease. J Parkinsons Dis. 2019;9(2). doi: 10.3233/JPD-191576