New Obesity Drug Candidate Shows Promise, Avoiding Gut-Related Side Effects of Current Treatments
Syracuse, NY – Researchers have identified a novel molecule, tridecaneuropeptide (TDN), that significantly reduced weight and improved metabolic health in animal models without the common nausea and vomiting experienced by patients taking popular GLP-1 based drugs like Ozempic. The breakthrough, published today in Science Translational Medicine, offers a potential new approach to obesity treatment by targeting brain support cells rather of neurons.
The Problem with Current Weight loss Drugs
The rising global obesity epidemic has fueled demand for effective weight loss solutions. GLP-1 receptor agonists, like semaglutide (Ozempic, Wegovy), have demonstrated remarkable success in promoting weight loss and improving blood sugar control. However, a meaningful drawback of these drugs is the prevalence of gastrointestinal side effects – nausea, vomiting, and diarrhea – which can lead to discontinuation of treatment for many patients. These side effects stem from the drugs’ action on neurons in the gut and brain, triggering a complex cascade of physiological responses.
A New Target: Brain Support Cells
A multidisciplinary team lead by Dr. Kevin Doyle at SUNY Upstate Medical university has taken a different tack. Instead of focusing on neurons, the researchers investigated the role of glial cells and astrocytes – support cells within the hindbrain – in regulating appetite and metabolism.
Their research revealed that these support cells naturally produce a molecule called octadecaneuropeptide (ODN). Direct injection of ODN into the brains of rats resulted in reduced appetite and improved glucose processing. Recognizing the impracticality of direct brain injections for human use, the team engineered a modified version, TDN, that can be administered via standard injection.
TDN: Promising Results in Animal Studies
Animal studies demonstrated that TDN effectively induced weight loss and improved insulin sensitivity in obese mice and musk shrews. Importantly, no animals experienced the gastrointestinal distress commonly associated with GLP-1 drugs.
The key difference lies in the mechanism of action. While GLP-1 drugs stimulate neurons, TDN activates downstream support cells that also influence hunger. Dr. Doyle explains this as “starting the race halfway through,” bypassing the initial neuronal cascade that triggers side effects. The goal is to directly impact the appetite suppression pathway without the extensive, and often unpleasant, physiological ripple effect.From Lab to Market: CoronationBio
To accelerate the development of TDN-based therapies, the researchers have co-founded a new biotechnology company, CoronationBio.The company has licensed intellectual property related to ODN derivatives from Syracuse University and the University of Pennsylvania and is actively collaborating with other pharmaceutical firms.
Looking Ahead
Human clinical trials are anticipated to begin as early as 2026 or 2027.If accomplished, TDN could offer a significantly better-tolerated treatment option for individuals struggling with obesity, possibly allowing for lower doses of existing GLP-1 drugs or providing a viable choice for those unable to tolerate their side effects.
Key Details:
Molecule: Tridecaneuropeptide (TDN), a modified version of octadecaneuropeptide (ODN). Mechanism of Action: Activates brain support cells (glia and astrocytes) to influence appetite, bypassing neurons and reducing side effects.
Animal Studies: Demonstrated weight loss and improved insulin sensitivity in obese mice and musk shrews without nausea or vomiting.
Company: CoronationBio,founded to develop TDN-based therapies. Human Trials: Projected to begin in 2026-2027.
Publication: Science translational Medicine – https://www.science.org/doi/10.1126/scitranslmed.adu6764
