How does exenatide work?
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.
Why is exenatide of interest for Parkinson’s?
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.
The results of this trial were presented to a group of the world’s top Parkinson’s experts at our annual meeting of the International Linked Clinical Trials (iLCT) committee. At that time, scores of existing medicines with potential for Parkinson’s were also evaluated; exenatide was singled out as the top priority for advancing into further clinical trials.
In 2017 the results of the larger, longer, and more robust phase 2 clinical trial of exenatide also showed a delay of motor symptom progression.
The results of the phase 2 trial were announced on 3 August 2017. Overnight, our goal of finding a cure for Parkinson’s was no longer considered to be fanciful, and people’s mindsets began to shift from ‘if’ to ‘when’Dr Simon Stott, Deputy Director of Research, Cure Parkinson’s
Around the world, there is great interest and research into exenatide and 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.