Exenatide and Parkinson’s
Exenatide and Parkinson’s: The history
Cure Parkinson’s has been at the forefront of exenatide’s journey as a potential treatment for Parkinson’s from the outset. We funded the first ever clinical study of exenatide in people with Parkinson’s. This was a year-long pilot study in 2008 involving 45 people with Parkinson’s – half of whom had twice-daily injections of exenatide on top of their normal medicines, half were part of the placebo or ‘dummy pill’ group. Those who took exenatide did not experience the decline in their movement that we normally see due to Parkinson’s. In fact, these participants improved a little. Crucially, some of these benefits were still present when measured one year after the participants had stopped taking exenatide, giving hope that this medicine had interfered with the underlying disease process, rather than simply masking symptoms.
Read more about the 2008 pilot study here
By 2008, the laboratory evidence for the brain-protective effects of exenatide had built up. Cure Parkinson’s already knew it was a safe medicine for humans, so it was relatively easy to test if it could help people with Parkinson’s.
We funded Professor Tom Foltynie and his team to run a small proof-of-concept trial at University College London. The 45 people who took part were between 45 and 70 years of age, and were all taking L-dopa medication for their Parkinson’s.
At the start of the trial, at six months, at one year and at 14 months, the volunteers’ motor symptoms (movements such as speech, tremor and walking) were assessed after pausing their medication the night before. By the end of the study the difference in Parkinson’s severity was modest but real; those taking exenatide had slightly improved, those not taking exenatide had slightly worsened .
With our support, Professor Foltynie assessed the study participants again, one year after the conclusion of the trial. He found that the motor symptoms of those who’d taken exenatide during the trial still had not worsened, while those who didn’t take exenatide during the trial had declined as expected in Parkinson’s .
Due to the size and design of the trial, this was not enough to conclude that exenatide was interrupting the progression of the disease in the brain, but it provided strong encouragement to look further. It led the iLCT committee to prioritise exenatide and influence the Parkinson’s research community to take exenatide forward.
Read more about the 2017 phase 2 clinical trial of exenatide
With Cure Parkinson’s encouragement and the backing of the iLCT committee, Professor Foltynie designed a phase 2 trial that would address the limitations of the first small pilot study of exenatide in people with Parkinson’s. This phase 2 trial was a double-blind placebo-controlled trial. That’s to say, neither those people taking part nor the researchers would know which of the participants were taking exenatide and which were taking a placebo (or dummy drug), until the end of the study.
Between June 2014 and March 2015, 62 people with Parkinson’s were enrolled in the study funded by US-based Michael J Fox Foundation for Parkinson’s Research. They were given either exenatide or placebo for 48 weeks. Their motor symptoms were assessed at the start of the study and again 12 weeks after finishing exenatide or placebo.
At 60 weeks, the group who had taken exenatide had a small improvement in their movement symptoms, while the group taking placebo had declined. The study results were published in the prestigious journal The Lancet.
GLP-1R agonists and Parkinson’s
Exenatide belongs to a group of drugs called glucagon-like peptide 1 receptor agonists (or GLP-1R agonists). GLP-1R agonists function by mimicking the action of GLP-1, a natural gut hormone produced in the stomach when food is consumed. GLP-1 stimulates insulin release from the pancreas into the bloodstream, which helps cells absorb glucose. Exenatide was the first GLP-1R agonist to be approved for the treatment of diabetes. Importantly, GLP-1R agonists have beneficial actions in the brain.
In tests in the laboratory, exenatide has shown to support dopamine brain cell (or neuron) function; reducing inflammation, improving neuron energy function and ‘switching on’ neuron survival signals. Researchers are now investigating if all of these effects can also occur in people with Parkinson’s in a clinical trial, while simultaneously assessing the impact of GLP-1R agonists on the day-to-day symptoms and progression of the condition.
Around the world, there is great interest and research into other GLP-1R agonist medicines including liraglutide and lixisenatide.
Cure Parkinson’s continues to drive these research efforts forward, and to ensure that if GLP-1R agonists prove to slow the progression of Parkinson’s, these drugs become available to people with Parkinson’s as quickly as possible.
Professor Tom Foltynie presents on the Exenatide PD3 trial at our Research Update Meeting