Stanford researchers use AI to discover naturally occurring molecule BRP that mimics Ozempic without common side effects

Stanford Medicine researchers used an AI algorithm called Peptide Predictor to discover BRP, a naturally occurring 12-amino-acid peptide that mimics the appetite-suppressing effects of Ozempic. In animal models, BRP reduced food intake by up to 50% and promoted fat loss without causing common side effects like nausea, constipation, or muscle loss. This favorable profile is attributed to BRP specifically targeting the hypothalamus rather than receptors throughout the digestive tract. While promising, the experimental molecule must undergo clinical trials to establish its safety and efficacy in humans.

BRP peptide discovery mechanism

• ▪Stanford Medicine researchers identified a naturally occurring 12-amino-acid peptide named BRP that suppresses appetite and reduces body weight in animal models.
• ▪The BRP peptide is derived from its parent prohormone BRINP2, also known as retinoic acid inducible neural specific 2.
• ▪In laboratory tests on neuron-like cells, the BRP peptide increased neuronal activity tenfold compared to untreated control cells.

AI-driven peptide identification

• ▪Stanford Medicine researchers developed a computer algorithm called Peptide Predictor to search human protein-coding genes for prohormone convertase cleavage sites.
• ▪The Peptide Predictor algorithm analyzed approximately 20,000 human protein-coding genes, narrowing the search to 373 prohormones and predicting 2,683 distinct peptides.

Animal study efficacy results

• ▪A single intramuscular injection of BRP reduced food intake by up to 50% during the following hour in both lean mice and minipigs.
• ▪BRP-treated mice demonstrated improved glucose tolerance and an enhanced response to insulin compared to control groups.
• ▪Obese mice treated with daily BRP injections for 14 days lost an average of 3 grams, primarily consisting of body fat.

Side effect profile comparison

• ▪Animal behavioral testing of BRP showed no significant signs of nausea, constipation, food aversion, or substantial loss of muscle mass.
• ▪Unlike semaglutide, which targets receptors in the gut, pancreas, and other tissues, BRP appears to act specifically in the hypothalamus.

Clinical development challenges

• ▪Katrin Svensson co-founded Merrifield Therapeutics, a company that plans to initiate human clinical trials for BRP in the near future.
• ▪Because small peptides degrade rapidly in the body, researchers are investigating methods to prolong the active duration of BRP.
• ▪Researchers have not yet identified the specific cell-surface receptor to which the BRP peptide binds.