In medicine, researchers often find that a drug intended for one use is also effective in different, unexpected ways.
In a recent study, researchers from University College London (UCL) found that exenatide — a medication that’s been approved by the Food and Drug Administration (FDA) since 2005 for people with type 2 diabetes — has the potential to modify Parkinson’s disease.
The study, published in the Lancet and funded by the Michael J. Fox Foundation for Parkinson’s Research (MJFF), had researchers testing exenatide in people with Parkinson’s.
In a test that pitted exenatide versus a placebo, researchers found that those who were taking exenatide had better motor function after their treatment.
This improvement persisted after a 12-week follow-up. For those who had taken a placebo, motor function showed a marked decline.
The findings have promising implications for people with Parkinson’s disease, a long-term degenerative condition for which there is currently no cure.
From lizard saliva to Parkinson’s treatment
Exenatide has an interesting history.
Dr. Dilan Athauda, first author of the UCL study, described the drug’s past in an email to Healthline. Athauda is a specialist registrar in neurology and a clinical research fellow at the National Hospital for Neurology and Neurosurgery.
“Exenatide is a synthetic version of a naturally occurring protein — exendin-4 — that was originally discovered by Dr. John Eng in the early 1990s in the saliva of the Gila monster, a venomous lizard native to the Southwestern United States,” he wrote.
Eng’s team found that exendin-4 was similar to a human hormone, glucagon-like peptide-1 (GLP-1). The substance is secreted in humans after eating a meal to stimulate insulin secretion, which lowers blood sugar.
In humans, GLP-1 quickly breaks down and its effects don’t last long. But studies showed the effects of exendin-4 (the Gila monster protein) lasted longer in humans.
This eventually led to approval from the FDA for the synthetic version of this protein — exenatide — for those with type 2 diabetes.
During the trials on its road to FDA approval, researchers found that exendin-4 had neuroprotective properties. This could help rescue degenerating cells and protect neurons.
Based on this preclinical evidence, Professor Tom Foltynie of the UCL Institute of Neurology supervised a small trial of exenatide in people with Parkinson’s.
“The team found that patients treated with exenatide for one year (in addition to their usual medication) had less decline in their motor symptoms when assessed without their medication compared to the control group (just on their usual medication) and this advantage over the control group was still present one year after stopping exenatide injections,” wrote Athauda.
Based on these results, the UCL team expanded their research and conducted a larger, double-blind, placebo-controlled trial.
Athauda told Healthline that patients treated with exenatide showed a reduced rate of decline compared with those who had taken a placebo.
He cautioned, however, that patients did not notice any difference in their quality of life.
Still, the findings show promise. UCL researchers would like to expand their research to include a larger group of participants across multiple centers.
Since Parkinson’s disease progresses slowly, Athauda notes that longer-term studies could give a clearer idea of how exenatide works with these patients.
“Overall, I think the results support accumulating data that this drug (and class of drugs) should be the subject of further investigation to assess their potential as a future therapy for Parkinson’s disease,” he wrote.
Some cautions with drug repurposing
“Using exenatide as a potential treatment for Parkinson’s disease is an example of drug repurposing or repositioning, and is an important pathway to bring new treatments to patients in a timely and cost-effective manner, however it is an inexact science,” wrote Athauda.
Exenatide has been FDA-approved for diabetes for years, and it has an excellent track record. But it does have some adverse side effects in people with Parkinson’s. These are mostly gastrointestinal issues like nausea and constipation.
“While we are optimistic about the results of our trial, there is more investigation to be done, and it will be a number of years before a new treatment could be approved and ready for use,” said Athauda in a release.
The results of the UCL study show promise, but the road to clinical approval is a long one.
“Using approved therapies for one condition to treat another, or drug repurposing, offers new avenues to speed Parkinson’s therapeutic development,” said Dr. Brian Fiske, senior vice president of research programs at MJFF, in a release. “The results from the exenatide studies justify continued testing, but clinicians and patients are urged not to add exenatide to their regiments until more is known about their safety and impact on Parkinson’s.”