Current weight-loss and diabetes medications, such as GLP-1 drugs, often fail to deliver lasting results and are plagued by unpleasant side effects.
These drugs work by targeting neurons in the brain’s hindbrain to control appetite—but nausea and vomiting cause up to 70% of patients to abandon treatment within a year.
A research team led by Robert Doyle, a chemistry professor at Syracuse University, has identified a promising alternative: targeting support cells in the brain rather than neurons.
This could help patients lose weight and improve blood sugar control without the gastrointestinal distress linked to existing treatments.
Neurons have long been the primary focus of brain research and drug development. GLP-1 medications act on these nerve cells to regulate hunger signals.
But Doyle’s team turned their attention to the brain’s “support” cells—such as glia and astrocytes—which help neurons function.
“Think of a neuron as a light bulb,” Doyle explained. “The support cells are everything that makes it shine—wiring, switches, filaments. They all play a role in how bright that bulb can be.”
The team discovered that certain support cells in the hindbrain naturally produce octadecaneuropeptide (ODN), a molecule that suppresses appetite. In lab experiments, injecting ODN directly into rats’ brains reduced their weight and improved glucose processing.
Because injecting molecules directly into the brain isn’t realistic for patients, the researchers engineered a modified version of ODN called tridecaneuropeptide (TDN). This new molecule can be given through routine injections, similar to drugs like Ozempic.
When tested in obese mice and musk shrews, TDN produced weight loss and improved insulin response—without triggering nausea or vomiting.
Cutting the “Marathon” Short
GLP-1 drugs work by setting off a long chain of chemical signals starting in neurons. TDN takes a shortcut, targeting the downstream processes in support cells that also produce appetite suppression—bypassing the steps that cause side effects.
“Instead of running a marathon from the starting line, we’re starting halfway through,” Doyle said. “By hitting the downstream process directly, we could avoid GLP-1’s side effects or reduce its dosage while keeping the benefits.”
To bring this discovery to market, a new company—CoronationBio—has licensed the intellectual property from Syracuse University and the University of Pennsylvania. The company aims to advance ODN-based treatments for obesity and cardio-metabolic diseases, with human clinical trials planned for 2026 or 2027.
If successful, this approach could transform obesity treatment, offering an effective, better-tolerated alternative to today’s GLP-1 medications.
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The study is published in Science Translational Medicine.
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