GLP-1 receptor agonists as a therapeutic opportunity in Parkinson’s disease

Parkinson’s disease (PD) is a brain disorder that causes movement problems and gradually worsens over time. It affects about 2% of people over the age of 60. Many people with PD—up to 80%—also have issues with how their bodies manage blood sugar, a condition called insulin resistance, which is also common in type 2 diabetes. Some inherited forms of PD are linked to changes in a gene called LRRK2. People with this mutation often show both movement symptoms and signs of insulin resistance. In our study, we used mice with the LRRK2 mutation and found both motor problems and signs of impaired insulin function (altered insulin release and action), similar to what is seen in human PD. Insulin resistance is connected to brain changes seen in PD, such as inflammation, nerve cell damage, and problems with energy production in cells. This suggests that improving insulin function could help protect the brain. Drugs called GLP-1 receptor agonists, already used to treat type 2 diabetes, help the body to manage blood sugar. They have also shown promise in improving symptoms in PD patients. However, it is still unclear how they protect the brain and whether it’s more important for these drugs to act inside the brain or elsewhere in the body. Our project aims to test two GLP-1 drugs—lixisenatide and semaglutide—in mice with the LRRK2 mutation to better understand how they work, and which could be more effective for treating Parkinson’s disease.