In 1817, James Parkinson expressed hope about the disease named after him. He thought that at some point there would be a discovery and “the progression 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 has reported the first glimmer of success – a modest disease progression in a one-year study.
And the medicine they used? A so-called GLP-1 receptor agonist, similar to the popular drugs Ozempic, for diabetes, and Wegovy, for obesity.
As much as half a million Americans are being 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. That can lead to difficulty walking, speaking and swallowing. Many patients develop dementia.
But there are medications and treatments, such as deep brain stimulation, that help, says Dr. David Standaert, a Parkinson’s expert at the University of Alabama at Birmingham.
“You’ll look and feel better,” says Dr. Standard. The problem is that the disease inevitably progresses.
“When you get five or 10 years into Parkinson’s, a lot of problems come up,” he said.
The new study gives researchers cautious hope.
It’s not a slam dunk, but it’s “nibbling at the edges of disease change,” says Dr. Michael S. Okun, a Parkinson’s disease expert 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 have been so many trials that have not shown success,” he added.
said Dr. Hyun Joo Cho at the National Institute of Neurological Disorders and Stroke that the study is “very important” but cautioned that it is a Phase 2 study, designed to test a hypothesis but not large enough or long enough to be specific.
“There are many examples of very promising Phase 2 trials,” he said. “People get excited, and then it never ends.”
The paper, published Wednesday in The New England Journal of Medicine, involved 156 people with early Parkinson’s disease who were randomly assigned to take the drug – lixisenatide, made by Sanofi – or a placebo and were followed for a year. The trial was funded by the French government and Cure Parkinson’s, a British charity.
During that time, Parkinson’s symptoms such as tremors, stiffness, slowness and balance worsened in those taking the placebo but not in those taking the drug.
The drug also caused gastrointestinal side effects such as nausea and vomiting in more than half of the participants, possibly because the researchers started at the highest dose rather than gradually increasing it as is done with GLP drugs. -1 like Ozempic or Wegovy. In a third of the participants, whose side effects became intolerable, the researchers divided their dose.
For European researchers, led by Dr. Wassilios G. Meissner of the University of Bordeaux and Dr. Olivier Rascol of the University of Toulouse, it makes sense to see if a GLP-1 drug can slow down Parkinson’s.
Studies have repeatedly found that people with Type 2 diabetes are at increased risk for Parkinson’s disease, said Dr. Rascol. But the increased risk decreases in those who take GLP-1 drugs to treat their diabetes.
He added that post-mortem studies of brain tissue from Parkinson’s patients found abnormalities related to 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 can affect the brain in different ways.
The French group said it wants to do larger and longer studies if it gets funding, and if it gets more of the drug. At the beginning of this year, Sanofi withdrew the drug in the US and said it had begun withdrawing it worldwide. The move was made for business reasons, a company spokesperson said.
But what about Parkinson’s patients with diabetes or obesity? They qualify for a GLP-1 drug. Should they take one in the hope that it will slow their Parkinson’s?
“It’s reasonable” for them to take the drugs, said Dr. Standaert, who wrote a editorial study partner.
But, he warns, they won’t know if the drugs have slowed the progression of their disease because they won’t know what would have happened if they hadn’t taken them.
“We can’t learn anything from this,” he said.
