Diabetes Drug Exenatide Shows Promise against Parkinson’s Disease

Exenatide, a drug commonly used to treat Type 2 diabetes, may have disease-modifying potential to treat Parkinson’s disease, according to new research from University College London.

ANCOVA (analysis of covariance) comparing decline in DaTscan (electrocardiographic and single photon emission CT) binding between the placebo and exenatide groups: (A) placebo group: reduced DaTscan binding in the left caudate, right caudate, and left putamen; (B) exenatide group: reduced DaTscan binding in the left caudate and right caudate; (C) significant clusters derived from the first level of analysis used to do an ANCOVA between placebo and exenatide groups showing a reduced rate of decline in the right caudate, left putamen, and right putamen. Image credit: Athauda et al, doi: 10.1016/S0140-6736(17)31585-4.

Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a synthetic version of exendin-4, a naturally occurring analogue of human GLP-1 that was originally discovered in the saliva of the Gila monster (Heloderma suspectum).

It activates receptors for the GLP-1 hormone in the pancreas to stimulate insulin release and was approved by the FDA in 2005 for patients whose diabetes was not well-controlled on other oral medication.

Prior evidence in animal models demonstrated that exenatide improved motor performance. Another study also found early evidence that it could be a disease-modifying agent for Parkinson’s disease, but it was an open-label trial.

The new study, published in the journal Lancet, strengthens the existing evidence as the first randomized, placebo-controlled trial of the drug for Parkinson’s patients.

“This is a very promising finding, as the drug holds potential to affect the course of the disease itself, and not merely the symptoms,” said senior author Professor Tom Foltynie, of the University College London Institute of Neurology.

“With existing treatments, we can relieve most of the symptoms for some years, but the disease continues to worsen.”

In the study, Professor Foltynie and co-authors followed 60 people with Parkinson’s disease at the UK’s National Hospital for Neurology and Neurosurgery as they used either a once-weekly injection of exenatide for 48 weeks, or a placebo, in addition to their regular medications.

They found that people who used exenatide had better motor function at 48 weeks when they came off the treatment, which persisted after the 12-week follow-up.

Those who had injected the placebo showed a decline in their motor scores at both the 48- and 60-week tests.

The advantage of 4 points, on a 132-point scale of measures such as tremors, agility and speech, was statistically significant.

The participants did not report noticeable improvements in their symptoms during the trial period beyond what their standard medication already did for them.

They were tested while temporarily off all medication, to determine how the disease itself was progressing.

The study did not determine conclusively whether the drug was modifying the disease itself, so the next stage in the research will investigate that more fully.

“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 first author Dr. Dilan Athauda, also from the University College London Institute of Neurology.

“We also hope to learn why exenatide appears to work better for some patients than for others.”

The team’s next step will be a longer-term study with more participants, which will investigate whether there are marked improvements in quality of life.

_____

Dilan Athauda et al. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet, published online August 3, 2017; doi: 10.1016/S0140-6736(17)31585-4