New Gut-Brain Signaling Drug Targets Prader-Willi Syndrome with Dr. Tien Lee Aardvark Therapeutics TRANSCRIPT

Dr. Tien Lee, Founder and CEO of Aardvark Therapeutics, draws a clear distinction between appetite and hunger and the implications for treating metabolic conditions and managing weight. The Aardvark lead drug candidate, an oral bitter taste receptor agonist designed to activate the gut-brain connection to turn off hunger, is showing effectiveness in treating Prader-Willi Syndrome and general obesity.  There are also signs that this drug could be effective for those using GLP-1s to avoid nausea and prevent rebound weight gain experienced after discontinuing GLP-1 drugs.

Tien explains, "That difference between hunger and appetite is the central thesis for our entire company, and your brain actually regulates how much you should eat. And it's driven by both appetite and hunger. So appetites like the carrot, and hunger is like the stick. Appetite is what you feel when you really enjoy a certain food, like ice cream or cake. And the appeal and the deliciousness of that food is a reward that your brain chases. Hunger is the feeling that you get when you have fasted for a prolonged period of time, and it really bothers you, and you feel real discomfort from not eating. And then at that point, food quality matters less, and you just want to escape that negative sensation. And we believe a lot of the current drugs are good at reducing appetite, but they don't so much address hunger like what our approach is pursuing." 

"In obesity, there's probably a combination of both appetite and hunger at play. And they're both important. In fact, your body has both appetite and hunger that are regulated. And when we eat food, our gut releases a number of gut hormones that help tamp down and give us satiety for both appetite and hunger. However, there are certain conditions where hunger is the predominant issue. And with the disease that is our lead indication is a condition called Prader-Willi syndrome. It's a rare genetic disorder that affects about one out of 15,000 live births. And patients with this condition have this unabated, unrelenting hunger that they feel that really starts to manifest when they're about four or seven years old. And then characteristically, patients will even feel compelled to eat garbage to the point of stomach rupture if unregulated with their food access. So it's a very debilitating condition with a lot of suffering for the patients and their families."  

"There are actually quite a number of new revelations in the scientific literature, and there's a greater appreciation of gut-brain signaling. So there are actually as many neurons in your gut as there are in your spinal cord, almost as many neurons as in the cat brain. And there's a greater appreciation of a two-way communication between your brain and the gut. So the vagus nerve is the largest nerve in your body, and there's actually a two-way communication between the gut and the brain. About 80% to 90% of the signal is actually from the gut to the brain. And even the drugs that people know currently, the Ozempic and the Zepbound drugs, are working through this gut path hormone. But naturally, a lot of the signals actually come from the gut to the brain through this vagus nerve conduction."

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