In 1817 James Parkinson expressed hope about the disease that bears his name. He thought that sooner or later there would be a discovery and “the progress of the disease could be stopped”.
Now, nearly 200 years since Parkinson expressed his hope, and after four decades of unsuccessful clinical trials, a group of French researchers reports 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.
About 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, stiffness and difficulty with balance. This 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, said Dr. David Standaert, a Parkinson's expert at the University of Alabama at Birmingham.
“You will look and feel much better,” Dr. Standaert said. The problem is that the disease progresses inexorably.
“When you have Parkinson's disease for five or 10 years, a lot of problems emerge,” he said.
The new study gave researchers cautious hope.
This is not a landslide victory, but “gnawing at the edges of disease modification,” said 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 study, said it was “a really encouraging step forward”.
“There have been so many studies that haven't shown success,” he added.
Dr. Hyun Joo Cho of the National Institute of Neurological Disorders and Stroke said the study is “very important,” but cautioned that it is a Phase 2 study, designed to test a hypothesis but not big enough or long enough to be definitive.
“There are so many examples of very promising Phase 2 studies,” he said. “People get very emotional, and then things don't work out.”
The paper, published Wednesday in the New England Journal of Medicine, involved 156 people with early-stage Parkinson's disease who were randomly assigned to take the drug – lixisenatide, made by Sanofi – or a placebo and followed for a year . The study was funded by the French government and Cure Parkinson's, a British charity.
During that time, Parkinson's symptoms such as tremor, stiffness, slowness and balance worsened in subjects 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, perhaps because researchers started with the highest dose instead of gradually increasing it as is done with GLP-1 drugs such as Ozempic or Wegovy. In a third of participants whose side effects had become intolerable, the researchers halved the 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 made sense to see whether a GLP-1 drug could slow Parkinson's.
Studies have repeatedly found that people with type 2 diabetes are at greater risk of developing Parkinson's disease, Dr. Rascol said. But this increased risk diminishes in those who take a GLP-1 drug to treat diabetes.
He added that post-mortem studies of brain tissue from Parkinson's patients had detected abnormalities linked to insulin resistance, even though the patients did not have diabetes. GLP-1 drugs treat insulin resistance.
Finally, he said, GLP-1 drugs can bind to proteins in neurons, so they can affect the brain in different ways.
The French group says it wants to do a larger, longer study if it can get funding and if it can get a larger amount of the drug. Earlier this year, Sanofi withdrew the drug from the United States and said it had begun recalling it worldwide. The move was made for business reasons, a company spokesperson said.
But what about Parkinson's patients who suffer from diabetes or obesity? They are entitled to a GLP-1 drug. Should they get one in the hope that it will slow their Parkinson's?
“It is reasonable” for them to take the drugs, said Dr. Standaert, who wrote an editorial accompanying the study.
But, he warned, they won't be able to tell 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 won't learn anything from this,” he said.