How treatment developed
1817
James Parkinson describes the condition
The London physician James Parkinson publishes An Essay on the Shaking Palsy, the first systematic description of the illness that now carries his name. Historians of the field note that effective drug treatment then took another 150 years to arrive.
1957 to 1960
Dopamine is linked to movement
In 1957 Arvid Carlsson shows that levodopa can relieve the immobility caused by reserpine in animals, and that reserpine empties the brain of dopamine while levodopa restores it. In 1960 Oleh Hornykiewicz reports a marked loss of dopamine in the striatum of people who had Parkinson's disease.
1961
The first levodopa injections
Walther Birkmayer and Hornykiewicz give levodopa intravenously to people with Parkinson's in Vienna and report a striking effect on movement, the first clinical demonstration of dopamine replacement.
16 February 1967
High dose oral levodopa
George Cotzias and colleagues report in the New England Journal of Medicine that gradually increased, high doses of oral levodopa produce a dramatic improvement in Parkinson's disease. A second drug, carbidopa, which blocks the breakdown of levodopa outside the brain, becomes a key part of the treatment in the years that follow.
18 December 2018
Focused ultrasound approved in the United States
The US Food and Drug Administration approves MRI guided focused ultrasound for tremor dominant Parkinson's disease, based on a randomised trial of 27 people in which 20 had the procedure and 7 had a sham procedure. The approval sits alongside deep brain stimulation as a surgical option that manages symptoms. It does not slow the underlying disease.
What conventional treatment has not solved
More than half a century after Cotzias, levodopa is still described as the most effective drug treatment for the movement symptoms of Parkinson's. The treatments that have followed, from newer drug combinations to pumps, deep brain stimulation and focused ultrasound, have mostly improved how well symptoms are managed.
What none of them has done is slow the disease itself. Reporting on the large UK platform trial launched in 2025 puts it plainly: there are no disease modifying treatments that can slow, stop or reverse the progression of Parkinson's. That gap is the backdrop to the research below, where scientists have tested whether molecules that protect nerve cells, including peptides and growth factors, can change the course of the condition.
The peptide and growth factor research, study by study
2003
GDNF delivered into the brain's fluid spaces: no benefit
GDNF is a growth factor protein that supports dopamine neurons in laboratory and animal studies. In a randomised, double blind trial in advanced Parkinson's, GDNF was given through an implanted catheter into the fluid spaces of the brain. The trial found no therapeutic benefit, and low blood sodium developed in more than half of the people who received doses of 75 micrograms or more. An open label extension, which followed 16 people for up to a further 20 months, also showed no benefit.
May 2013
Exenatide: the first small trial in Parkinson's
A University College London team led by Thomas Foltynie runs a single blind study of 45 people with moderate Parkinson's. Half receive the diabetes drug exenatide, a GLP-1 receptor agonist, by injection for 12 months, and half act as controls. Blinded video ratings of the motor score improved by 2.7 points in the exenatide group and worsened by 2.2 points in controls, a difference of 4.9 points (95% confidence interval 0.3 to 9.4). The authors describe it as a proof of concept, and weight loss was common in the exenatide group. The study was funded by the Cure Parkinson's Trust.
August 2017
Exenatide: the first placebo controlled trial
The Lancet publishes a single centre, double blind trial of 62 people with moderate Parkinson's, 32 given exenatide 2 mg once a week and 30 given placebo for 48 weeks. After a 12 week washout, the off medication motor score had improved by 1.0 point in the exenatide group and worsened by 2.1 points on placebo, an adjusted difference of 3.5 points (95% confidence interval 0.3 to 6.7, p = 0.0318). Six serious adverse events occurred in the exenatide group and two in the placebo group. The authors said it was unclear whether exenatide changes the underlying disease or has a lasting symptomatic effect. The trial was funded by the Michael J Fox Foundation.
February 2019
GDNF infused directly into the putamen: primary goal missed, brain scans changed
A Bristol team led by Alan Whone reports a randomised, double blind trial of GDNF given directly into the putamen every four weeks for 40 weeks through a skull mounted port. Forty one people took part, 6 in a pilot stage and 35 in the main stage, receiving 120 micrograms per putamen. The primary goal, the percentage change in the off medication motor score at week 40, was not met: the score fell by 17.3% in the GDNF group and 11.8% on placebo, a difference of 4.9% (p = 0.41). Brain imaging told a different story, with dopamine tracer uptake rising by between 25% and 100% in parts of the putamen in the GDNF group.
In an 80 week open label extension in which all 41 people received GDNF, the motor score fell by 26.7% in those on GDNF throughout and 27.6% in those switched from placebo. The authors concluded that future GDNF testing would probably need a longer treatment period, a higher dose, or both.