In 1817, James Parkinson expressed hope for the disease that bears his name. He thought that at some point a discovery would be made and “the progress of the disease might be stopped.”
Now, almost 200 years since Parkinson expressed his hope and after four decades of unsuccessful clinical trials, a team of French researchers is reporting the first glimmer of success – a modest slowing of the disease in a year-long study.
And the drug they used? A so-called GLP-1 receptor agonist, similar to the hugely popular drugs Ozempic, for diabetes, and Wegovy, for obesity.
Up to half a million Americans have been diagnosed with Parkinson’s disease, a degenerative brain disease second only to Alzheimer’s in prevalence.
Symptoms include tremors, slowness and stiffness, and difficulty with balance. This can lead to difficulty walking, speaking and swallowing. Many patients develop dementia.
But there are drugs and treatments, such as deep brain stimulation, that help, said Dr. David Standaert, a Parkinson’s specialist at the University of Alabama at Birmingham.
“You will look and feel much better,” said Dr. Standaert. The problem is that the disease progresses inexorably.
“When you get five or ten years into Parkinson’s, a lot of problems emerge,” he said.
The new study gave researchers cautious hope.
It’s not a slam dunk, but “it nibbles at the edges of disease modification,” said Dr. Michael S. Okun, a Parkinson’s specialist at the University of Florida who was not involved in the study.
Dr Standaert, who was also not involved in the trial, said it was “a really encouraging step forward”.
“There were so many tests that were not successful,” he added.
Dr. Hyun Joo Cho at the National Institute of Neurological Disorders and Stroke said the study was “very important,” but cautioned that it was a Phase 2 study, designed to test a hypothesis but not large enough or big enough to be definitive.
“There are many, many examples of very promising Phase 2 trials,” he said. “People get really excited and then it doesn’t come out.”
The work, published Wednesday in The New England Journal of Medicine, involved 156 people with early Parkinson’s disease who were randomly assigned to receive the drug — lixisenatide, produced by Sanofi — or a placebo and followed for a year. The trial was funded by the French government and Cure Parkinson’s, a British charity.
During this time, Parkinson’s symptoms such as tremors, stiffness, slowness and balance worsened in those who received the placebo, but not in those who received the drug.
The drug also caused gastrointestinal side effects such as nausea and vomiting in more than half of the participants, perhaps because the researchers started with the highest dose rather than gradually increasing it as is done with GLP-1 drugs such as Ozempic or Wegovy. In a third of the participants whose side effects became intolerable, the researchers cut their dose in half.
For the European researchers, led by Dr. Wassilios G. Meissner of the University of Bordeaux and Dr. Olivier Rascol of the University of Toulouse, it made sense to see if a GLP-1 drug could slow down Parkinson’s disease.
Studies have repeatedly found that people with type 2 diabetes are at increased risk for Parkinson’s disease, Dr. Rascol said. But this increased risk is reduced in those taking a GLP-1 drug to treat their diabetes.
He added that postmortem studies of brain tissue from Parkinson’s patients had found abnormalities associated with insulin resistance, even though the patients did not have diabetes. GLP-1 drugs treat insulin resistance.
Finally, he said, GLP-1 drugs can attach to proteins in neurons, so they may affect the brain in different ways.
The French group says it wants to do a bigger and bigger study if it can get funding and if it can get more of the drug. Earlier this year, Sanofi withdrew the drug in the US and said it has begun withdrawing it globally. The move was made for business reasons, a company spokesperson said.
But what about Parkinson’s patients who have diabetes or obesity? They are eligible for a GLP-1 drug. Should they take one in the hope that it will slow Parkinson’s?
“It makes sense” for them to take the drugs, said Dr. Standaert, who wrote an article accompanying the study.
But, he warned, they won’t be able to say whether the drugs slowed the progression of the disease because they won’t know what would have happened if they hadn’t taken them.
“We’re not going to learn anything from this,” he said.
