Thu. Jul 25th, 2024

An Ozempic Relative Slowed Parkinson’s Disease in a Small Study

In 1817, James Parkinson expressed a hope about the disease that is named after him. He thought that at some point there would be a discovery and “the progress of the disease may 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 one-year study.

And the drug they used? A so-called GLP-1 receptor agonist, similar to the wildly popular drugs Ozempic, for diabetes, and Wegovy, for obesity.

As many as half a million Americans have been diagnosed with Parkinson’s disease, a degenerative brain illness second only to Alzheimer’s in prevalence.

Symptoms include tremors, slowness and stiffness, and difficulty with balance. That can lead to difficulty walking, talking and swallowing. Many patients develop dementia.

But there are drugs and treatments, like 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 inexorably progresses.

“When you get five or 10 years into Parkinson’s, a lot of problems emerge,” he said.

The new study gave researchers cautious hope.

It is not a slam dunk, but it is “nibbling 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 also was not involved in the trial, said it was “a really encouraging step forward.”

“There were so many trials that showed no success,” 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 big enough or long enough to be definitive.

“There are many many examples of very promising Phase 2 trials,” she said. “People get very excited, and then it doesn’t pan out.”

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 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 like tremor, stiffness, slowness and balance worsened in those taking the placebo but not in those taking the drug.

The drug also caused gastrointestinal side effects like nausea and vomiting in more than half of the participants, perhaps because the researchers started with the highest dose instead of gradually increasing it as is done with GLP-1 drugs like Ozempic or Wegovy. In a third of participants, whose side effects became intolerable, the researchers halved their dose.

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 Parkinson’s.

Studies have repeatedly found that people with Type 2 diabetes are at increased risk for Parkinson’s disease, Dr. Rascol said. But that increased risk declines in those who take a GLP-1 drug to treat their diabetes.

He added that post-mortem studies of brain tissue from Parkinson’s patients had 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 may affect the brain in different ways.

The French group says it wants to do a larger and longer study if it can get funding, and if it can get more of the drug. At the start of this year, Sanofi withdrew the drug in the U.S. and said it has started withdrawing it worldwide. The move was made for business reasons, a company spokesman 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 hopes 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 cautioned, they will not be able to tell if the drugs have caused their disease progression to slow because they won’t know what would have happened if they had not taken it.

“We won’t learn anything from it,” he said.

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