Q&A with Caroline Geisler: Exploring new path to weight loss — minus side effects

LEXINGTON, Ky. (Aug. 11, 2025) — The most effective obesity medications of today — GLP-1 medications such as Ozempic and Wegovy — can come with significant side effects, most commonly nausea and vomiting. Caroline Geisler, Ph.D., assistant professor in the University of Kentucky College of Pharmacy Department of Pharmaceutical Sciences, and her team wanted to explore whether a different signaling system in the brain could be targeted to achieve weight loss and blood sugar control without triggering those unpleasant symptoms. 

Geisler breaks down findings from the study published in the journal Science Translational Medicine in this Q&A:

UKNow: What exactly did you discover? 
Geisler: Our research focused on a small peptide in the brain called octadecaneuropeptide (ODN), produced by glial cells — all the non-neuron cells that keep the brain working properly. ODN is naturally recruited after a meal and helps regulate hunger and metabolism. We wondered whether mimicking ODN signaling could be therapeutically useful to improve metabolic health in obesity and diabetes. We showed that by activating this pathway in animal models, we were able to promote weight loss and improve blood sugar control without causing nausea, vomiting or changes in heart rate or body temperature. Importantly, this worked when a drug mimicking ODN signaling was given in the body, analogous to how many drugs are taken in people. 

UKNow: How is this different from drugs like Ozempic or Wegovy? 
Geisler: GLP-1 medications mimic a hormone that signals fullness but often interact with parts of the brain and digestive system that can trigger nausea. Our approach targets an entirely different brain pathway, involving glial cells in the hindbrain. In early animal studies, this new pathway was effective without the gastrointestinal side effects that commonly lead people to stop GLP-1 medications. This work and future studies on ODN will greatly enhance our understanding of how the brain, especially glial cells, sense and respond to metabolic challenges. 

UKNow: What is TDN, and why is it important? 
Geisler: TDN is a modified version of ODN that’s small enough to be delivered outside the brain — through a systemic injection, like how biologic drugs, including GLP-1 medications, are taken — and still reach its target. In our study, TDN caused weight loss in rodents, improved their blood sugar levels and — crucially — did not cause vomiting, nausea or other signs of discomfort in the animals. 

UKNow: Why does avoiding nausea matter so much? 
Geisler: It’s a significant issue. Up to 70% of patients taking GLP-1 therapies experience nausea and vomiting, which is a primary reason over half of patients stop taking GLP-1 medications. A treatment that’s equally effective but easier to tolerate could help far more people stick with it — and achieve better long-term health outcomes. We hope this alternate approach will fill the clinical gap for the population of patients who cannot tolerate GLP-1 therapies. 

UKNow: How does this new treatment work in the body? 
Geisler: In simple terms, it tells the brain, “You’ve had enough.” TDN copies the natural signaling of ODN from glial cells that help sense the body’s energy status. TDN tells the brain that the body has a surplus of energy and provides instructions about what to do with this excess energy. When activated, this pathway helps reduce hunger, improve how the body uses glucose and lower the signals that tell the liver to release sugar — all without the “alarm bells” that cause nausea. 

UKNow: Could this drug be used alongside existing treatments? 
Geisler: Potentially, yes. In fact, we found that when combined with GLP-1 medications in animal models, TDN appeared to enhance the effect without adding side effects. This opens the door to using TDN or future optimized ODN-based compounds as a standalone treatment or as part of combination therapy. 

UKNow: Is this ready for human use? 
Geisler: Not yet. These are early-stage preclinical findings. More research is needed to understand how this pathway works in humans and to ensure safety. However, we’re optimistic. This work has inspired the launch of a new company, CoronationBio, formed by a group of seed investors in collaboration with Syracuse University and the University of Pennsylvania. CoronationBio has licensed the intellectual property of ODN derivatives for the treatment of obesity and cardio-metabolic diseases and is continuing to work with me and other authors of this manuscript to translate drug candidates into the clinic.  

UKNow: What’s the timeline for this moving toward patients? 
Geisler: If all goes well, we hope to be at the stage to begin the first-in-human clinical trials within the next two to three years. Drug development takes time, but this study lays an exciting foundation. 

UKNow: What does this mean for the future of obesity treatment? 
Geisler: Despite the success of GLP-1 therapies, the clinical landscape for drugs to improve metabolic health is still wide open and seeking alternate approaches. This research points to a new class of weight-loss and diabetes medications that may offer the same — or hopefully even better — benefits as current drugs but without the harsh side effects. That could dramatically expand treatment options and help more people safely manage their weight and metabolic health. 

UKNow: What does this say about UK’s role in this kind of research? 
Geisler: This work is a great example of how the University of Kentucky contributes to national conversations around obesity, neuroscience and metabolism. It also shows the value of cross-institutional collaboration — we worked closely with researchers at the University of Pennsylvania, Syracuse University and our biotech partner, CoronationBio, to make this possible.

You can read the team's full study published in the journal Science Translational Medicine online.