In yet another surprise attribute of the new class of obesity drugs, scientists have found that GLP-1 receptor agonists can also subdue brain inflammation, giving them a potential ‘superpower’ in the fight against Alzheimer’s and Parkinson’s diseases.
Inflammation, which is highly prevalent in those with chronic metabolic diseases, is one of the hallmarks of both Alzheimer’s and Parkinson’s.
“One of the really interesting things about the GLP-1 drugs is that beyond the control of blood sugar and body weight, they also seem to reduce the complications of chronic metabolic disease,” said study co-author Daniel Drucker, a professor in the department of medicine at the University of Toronto. “We know from clinical studies that GLP-1 does all this amazing stuff in people, but we don’t fully know how it works.”
Glucagon-like peptide-1 (GLP-1) receptor agonists have become the most talked-about medical-science development since mRNA vaccines. Semaglutide and tirzepatide, known under brand names such as Ozempic, Wegovy and Mounjaro, were first used to effectively treat type 2 diabetes, but have since found fame as a new, highly touted class of weight-loss medication.
Drucker and team believed that this wasn’t the limit of their ‘superpowers’, and were keenly interested in the relationship between inflammation and GLP-1 drugs. What the researchers found was a new, fascinating and potentially life-changing interaction with other organs, but particularly the brain.
“The strange thing is that you can’t find many GLP-1 receptors in all these other organs where GLP-1 seems to work,” said Drucker, whose earlier work opened the door to the development of drugs including Ozempic and Wegovy.
The team found that in mice suffering inflammation – brought on by the immune system’s response to a bacterial cell wall component or bacterial slur – GLP-1 agonists reduced the condition, but only when the receptors in the brain weren’t blocked. This demonstrated a new way that GLP-1 drugs interacted with inflammation and the brain-immune system axis, independent of their other known benefits.
“As the scientific community deservingly celebrates GLP-1 agonists and their impact, there are many unknowns left,” said Anne-Claude Gingras, director of the Lunenfeld-Tanenbaum Research Institute. “Dr. Drucker and his team have remained tenacious in their efforts to unpack how these drugs work, and this study deepens our understanding of metabolism and the complex brain-immune network that regulates it.”
In Alzheimer’s and Parkinson’s disease, pathological proteins beta-amyloid and alpha-synuclein, respectively, interact with certain receptors to trigger many pathways of inflammation. Being able to mediate the activity of these proteins and receptors with a GLP-1 receptor agonist could provide an effective treatment of neuroinflammation in these degenerative diseases.
The team now hopes to establish which brain cells are interacting with GLP-1, as well as other models of inflammation in the heart, liver and kidney, which holds huge promise in treating related chronic diseases of those organs.
The study was published in the journal Cell Metabolism.
Source: University of Toronto