Brain Shortcut to Weight Loss: No Nausea – Science Breakthrough
Beyond Ozempic: A New Target for Weight Loss with Fewer Side Effects
For millions struggling with obesity and type 2 diabetes, medications like Ozempic and Zepbound offer hope, but often come with a notable drawback: unpleasant and debilitating side effects. A significant 70% of patients discontinue GLP-1 drugs within a year due to nausea and vomiting. Now, a team of researchers at Syracuse University is pioneering a novel approach to weight loss that bypasses the problematic pathways of current drugs, potentially offering a more tolerable and effective solution.
The Limitations of Current Treatments
GLP-1 drugs work by targeting neurons in the brain that control appetite. While effective for some, this neuronal focus is also the source of thier common side effects. Researchers are increasingly looking beyond neurons to “support” cells - glia and astrocytes – which play a crucial, yet often overlooked, role in brain function.
“We wanted to no whether support cells might produce new peptides or new signaling molecules that might be critical in body weight reduction,” explains Robert Doyle, a medicinal chemist and the Jack and Laura H. Milton Professor of Chemistry at Syracuse University,who also holds appointments at SUNY upstate Medical university.
Support Cells: The Unsung Heroes of Appetite Control
Doyle’s team discovered that these support cells in the hindbrain naturally produce a molecule called octadecaneuropeptide (ODN),which demonstrably suppresses appetite. In laboratory tests, direct injection of ODN into the brains of rats resulted in weight loss and improved glucose processing.
However, direct brain injection isn’t a viable treatment option for humans. the team addressed this challenge by engineering a new version of the molecule, tridecaneuropeptide (TDN), designed for management through regular injections, similar to existing GLP-1 medications.
TDN: A Shortcut to Weight Loss
Testing in obese mice and musk shrews revealed that TDN effectively promoted weight loss and improved insulin response without causing the nausea and vomiting associated with GLP-1 drugs. The key lies in how TDN works.
Doyle uses a simple analogy: “Think of each brain neuron as a light bulb and support cells as the components that allow the light bulb to brighten, including the wiring, switch and filament. All of those supporting parts beyond the light bulb play a role in making the light shine.”
Current drugs, like GLP-1s, initiate a complex cascade of reactions, a “marathon” of chemical signaling, to ultimately influence appetite. TDN, though, bypasses the neurons altogether, directly targeting the support cells and their appetite-suppressing capabilities.”Rather of running a marathon from the very beginning like current drugs do, our targeting downstream pathways in support cells is like starting the race halfway through, reducing the unpleasant side effects many people experience,” Doyle explains. “If we could hit that downstream process directly, then potentially we wouldn’t have to use GLP-1 drugs with their side effects. Or we could reduce their dose,improving the toleration of these drugs.”
From Lab to Clinic: CoronationBio and the Future of Obesity treatment
the promising research has spurred the launch of CoronationBio, a new company dedicated to translating this discovery into a real-world treatment. CoronationBio has licensed intellectual property related to ODN derivatives from Syracuse University and the university of Pennsylvania, and is actively seeking partnerships to accelerate progress.
Human trials are anticipated to begin as early as 2026 or 2027, offering a potential new horizon for individuals seeking lasting weight loss and improved metabolic health – one that prioritizes efficacy and tolerability.