Writer: Kiana Danesh Manesh
Editor: Isabello Io
What is Parkinson’s Disease?
Parkinson's is a neurodegenerative disease that worsens over time. The disease is characterized by the loss of nerve cells in the basal ganglia of the nervous system, which is responsible for controlling movement. The death of these nerve cells also impacts the production of dopamine, a neurotransmitter that is responsible for feelings of pleasure, learning and motivation. This creates symptoms such as shaking, unintended movement, and stiffness. The reduction in dopamine may also cause depression or other behavioral changes. Diabetes is also a risk factor for those with Parkinson’s, hence a diabetic person has a greater risk of developing Parkinson's.
There is no definite cure or treatment for Parkinson's disease, but there are options for patients to relieve the symptoms they are presented with. A common medicine which patients with Parkinson’s take is levodopa, which helps nerve cells produce dopamine that would otherwise slowly run out. However, this medicine causes severe adverse side effects, such as confusion, vomiting, loss of appetite, and hallucinations. (1) As an alternative, GLP-1 receptor agonists are emerging as possible treatments against Parkinson’s after multiple promising studies.
What are GLP-1 agonists?
GLP-1 (Glucagon-like protein-1) agonists are medications commonly used to treat type 2 diabetes by injection, aiming for lowered blood sugar levels and weight loss. It is a hormone that stimulates insulin release from the pancreas. This insulin then pushes out glucose in the bloodstream to the cells in the body, effectively reducing blood sugar levels. It also reduces appetite, which then leads to weight loss. GLP-1 drugs include Ozempic, Trulicity, and Byetta (to name a few). (2)
Study and Research
A promising 2024 study was conducted after a GLP-1 agonist receptor showed neuroprotective properties in a mouse model of Parkinson’s disease. A group of researchers based in France launched an investigation into the matter, the researchers attempted to determine the efficiency of GLP-1 agonists against the progression of Parkinson’s in 156 participants who were diagnosed with the disease 3 years prior, by putting a GLP-1 receptor agonist called lixisenatide against a placebo. (3) Participants were randomly assigned to a placebo or lixisenatide group and attempted that form of treatment for a span of 12 months, followed by a 2-month washout period (a period wherein no treatment is given). The researchers used the MDS-UPDRS (Movement Disorder Society - Unified Parkinson's Disease Rating Scale) to determine if there were improvements or not. At the beginning of the study, all participants started at 15 on the scale. At the end of the 12 months, they were rated on the scale again. The group assigned to the lixisenatide showed improvement in movement, as they had changed by -0.04 points on the scale, whereas the group assigned the placebo had worsened by 3.04 points. After the 2-month washout period, both groups had an increase in motor deficiency, but the results were still better in the lixisenatide group. However, the lixisenatide group reported more nausea and vomiting. This study has proven that GLP-1 agonists have strong anti-inflammatory effects. Researchers theorize that these neuroprotective effects in GLP-1 agonists prevent neuron loss in the brain, which means there is little dopamine loss. (4) There need to be further and longer trials conducted on lixisenatide to determine if it can truly be a candidate for treatment against Parkinson’s in the future, but so far it is promising.
In another study done by Thomas Foltynine and Iciar Aviles-Olmos, two neuroscientists at the University College London institute for neurology, 45 participants were assigned to either the exenatide (Byetta, a medication used for type 2 diabetes) group or the control group; participants knew what treatment was given. Like the study conducted with lixisenatide, this study was also carried out over a 12-month treatment period followed by a 2-month washout period. Participants were rated with both the MDS-UPDRS scale to test motor skills and the Mattis-DRS scale, a cognitive tool that assesses memory, attention, preservation and construction, to test cognitive ability. After the 14-month period, significant improvements were shown in the exenatide group, showing advancements in both cognitive (6.3 point difference) and motor (7.2 point difference) ability. Even after a 12-month washout period, the benefits of exenatide still persisted, suggesting that it may be more than a drug which can just be used for symptomatic relief. The drug was well-tolerated with the only adverse effect being weight loss, which did not impact the study. (5)
Conclusion
GLP-1 receptor agonists show great promise to be used as medication, not only for type 2 diabetes, but also for those with Parkinson’s and perhaps also for other neurodegenerative disorders in the near future. Trials done on medications such as exenatide and lixisenatide have shown the neuroprotective and anti-inflammatory effects that GLP-1 agonists hold, and how they slow down the progression of motor and even cognitive deficiency in those with Parkinson’s. Further trials and studies will have to be carried out on the effects and side effects of the drugs and how they perform in studies carried out for over one year before being approved as a drug used against the symptoms of Parkinson’s Disease. However, there is a lot of potential for GLP-1 agonists.
Sources & Works Cited
(1) National Institute on Aging. “Parkinson’s Disease: Causes, Symptoms, and Treatments.” National Institute on Aging, 14 Apr. 2022, www.nia.nih.gov/health/parkinsons-disease/parkinsons-disease-causes-symptoms-and-treatments#:~:text=Parkinson.
(2)ELS, Lisa Catanese. “GLP-1 Diabetes and Weight-Loss Drug Side Effects”: Harvard Health, 5 Feb. 2024, www.health.harvard.edu/staying-healthy/glp-1-diabetes-and-weight-loss-drug-side-effects-ozempic-face-and-more.
(3)Meissner, Wassilios G, et al. “Trial of Lixisenatide in Early Parkinson’s Disease.” the New England Journal of Medicine (Print), vol. 390, no. 13, 4 Apr. 2024, pp. 1176–1185, https://doi.org/10.1056/nejmoa2312323.
(4)Ko, Elizabeth, and Eve M. Glazier. “GLP-1 Medications May Slow Progression of Parkinson’s Symptoms.” Www.uclahealth.org, 6 May 2024, www.uclahealth.org/news/article/glp-1-medications-may-slow-progression-parkinsons-symptoms#:~:text=As%20with%20many%20chronic%20and. Accessed 25 May 2024.
(5)Foltynie, Thomas, and Iciar Aviles-Olmos. “Exenatide as a Potential Treatment for Patients with Parkinson’s Disease: First Steps into the Clinic.” Alzheimer’s & Dementia, vol. 10, no. 1, Feb. 2014, pp. S38–S46, https://doi.org/10.1016/j.jalz.2013.12.005. Accessed 4 June 2019.
(6)Kopp, Katherine O., et al. “Glucagon-like Peptide-1 (GLP-1) Receptor Agonists and Neuroinflammation: Implications for Neurodegenerative Disease Treatment.” Pharmacological Research, vol. 186, 1 Dec. 2022, p. 106550, www.sciencedirect.com/science/article/pii/S1043661822004960?via%3Dihub, https://doi.org/10.1016/j.phrs.2022.106550.
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