BRP natural Ozempic candidate found in Stanford AI search
Stanford Medicine says AI helped identify BRP, a natural peptide that reduced appetite and fat in animals without several Ozempic-like side effects.
By Lucas Ferreira · Science & Environment Writer
3 min read
Stanford Medicine researchers say an AI-assisted search has identified BRP, a natural Ozempic candidate that reduced appetite and body fat in animal studies. The finding matters because the peptide appeared to act through a more targeted brain pathway than semaglutide, the active ingredient in Ozempic, while avoiding several side effects seen with that drug in the experiments.
The research, published in Nature, describes BRP as a naturally occurring 12-amino-acid peptide linked to a prohormone called BRINP2. Stanford Medicine said the work was led by senior research scientist Laetitia Coassolo and senior author Katrin Svensson, an assistant professor of pathology.
What is BRP?
BRP is a small peptide, meaning a short chain of amino acids, that the Stanford team identified while looking for hidden hormone-like signals involved in appetite and metabolism. According to Stanford Medicine, it appears to affect the hypothalamus, a brain region that helps regulate hunger, energy use and related body functions.
That differs from semaglutide, which mimics GLP-1 and acts on receptors found in the brain as well as the gut, pancreas and other tissues. Svensson said that broad receptor pattern helps explain why Ozempic can slow digestion and affect blood sugar, while BRP appears to act more specifically in the hypothalamus.
How AI narrowed the search
The Stanford team used a computer program called Peptide Predictor to scan all 20,000 human protein-coding genes for likely cutting sites used by prohormone convertases. These enzymes cut inactive prohormones into smaller peptides, some of which can work as hormones.
The researchers focused on prohormone convertase 1/3, an enzyme previously associated with obesity in humans and also involved in producing GLP-1. Their screening narrowed the field to 373 prohormones and 2,683 possible peptides, according to Stanford Medicine.
Coassolo and Svensson then selected 100 peptides for cell testing, including GLP-1 as a comparison. GLP-1 increased activity in neuron-like cells to three times the level of untreated controls, while BRP increased activity tenfold, the researchers reported.
What happened in animal tests?
In lean mice and minipigs, an intramuscular BRP injection before feeding reduced food intake over the next hour by as much as 50%, according to Stanford Medicine. Minipigs were included because their metabolism and eating patterns more closely resemble those of humans than mice do.
In a 14-day test in obese mice, animals given daily BRP injections lost an average of 3 grams, with nearly all of the loss coming from fat. Control mice gained about 3 grams during the same period, and treated mice showed improved glucose and insulin tolerance.
Stanford Medicine said behavioral tests found no meaningful differences in movement, water intake, anxiety-like behavior or fecal output between treated and untreated animals. Researchers also did not observe nausea-related responses or major muscle loss in the BRP-treated animals.
What needs to happen before human use?
The results remain limited to animals. The Stanford team is trying to identify the cell-surface receptor that BRP binds to and to map the steps that follow after that binding occurs.
The researchers are also studying how to make BRP last longer in the body, since small peptides can break down quickly. Stanford Medicine said Svensson has co-founded Merrifield Therapeutics, which plans to begin human clinical trials of the molecule, and disclosed that Svensson and Coassolo are inventors on patents covering BRP peptides for metabolic disorders.
This story draws on original reporting from ScienceDaily.