Glucagon-like peptide 1 receptor (or GLP-1R) agonists are recognised as a frontline treatment for diabetes. Researchers have recently been developing the next generation of treatment for diabetes which target GLP-1R and another protein called gastric inhibitory polypeptide (or GIP) at the same time. These combination drugs are referred to as ‘dual agonists’. Now, in Cure Parkinson’s funded research, scientists are testing if dual agonists offer potential as a treatment for Parkinson’s.

GLP-1R and GIP agonists are drugs that mimic naturally occurring gut hormones which stimulate the release of insulin from the pancreas. GLP-1R agonists are widely used in the treatment of diabetes, helping the body to manage blood sugar levels. They have also been shown to have neuroprotective effects in the brain.

Exenatide is a GLP-1 agonist and in models of Parkinson’s, exenatide has shown to improve dopamine nerve cell function, reduce inflammation, improve energy production and switch on brain cell survival signals. Researchers are now trying to uncover if all of these effects also occur in humans, while simultaneously assessing exenatide’s impact on the day-to-day symptoms and progression of Parkinson’s.

GIP agonists are a new class of experimental drugs being developed for diabetes. They too have displayed neuroprotective properties in models of neurodegenerative conditions, which has led researchers to begin developing ‘dual agonists’, which combine the beneficial effects of both GLP-1R and GIP agonists.

Having played an important role in the phase 2 clinical trial of exenatide in Parkinson’s, Dr Dilan Athauda at University College, London will now assess the potential of using GLP-1R/GIP dual agonists as future treatments for Parkinson’s. Dual agonists are now being clinically tested for the treatment of diabetes, and Dr. Athauda will test this new class of drug in the laboratory using induced pluripotent stem cells (iPSC) to explore whether the GLP-1R and GIP agonists together are better at treating Parkinson’s than the GLP-1 receptor agonists alone. The project will test the best dual GLP/GIP agonist combination which can then, it is hoped, move into trials involving people with Parkinson’s as soon as possible.

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