Imma Perfetto
Cosmos science journalist
Pharmacologists have used artificial intelligence to discover a naturally occurring molecule in humans, which like the popular drug Ozempic, suppresses appetite and reduces body weight.
Tests to date have only been on animals but Katrin Svensson, assistant professor of pathology at Stanford University in the US, says nothing tested before has semaglutide’s ability to decrease appetite and body weight.
“We are very eager to learn if [it] is safe and effective in humans,” she says.
The molecule, named BRP, activates different neurons in the brain and acts through a separate, but similar, metabolic pathway to semaglutide – also known by its brand name Ozempic.
Initial tests in mice and pigs showed the new molecule doesn’t trigger some of semaglutide’s more uncomfortable side effects, such as nausea, constipation and significant loss of muscle mass.
“The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas and other tissues,” says Svensson, senior author of the Nature paper presenting the discovery.
“That’s why Ozempic has widespread effects including slowing the movement of food through the digestive tract and lowering blood sugar levels. In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism.”
Semaglutide works by mimicking glucagon-like peptide 1 (GLP-1), a naturally occurring hormone produced in the gut which stimulates insulin and urine production, slows the emptying of the stomach and reduces appetite.
The researchers designed an algorithm named Peptide Predictor to help identify other peptides which might also be involved in metabolism.
The team focused on peptides most likely to be biologically active in the brain, and screened 100 of them, including GLP-1, for their ability to activate lab-grown neuronal cells.
While GLP-1 increased the cells’ activity threefold, BRP bumped it up tenfold.
They tested its effects on mice and miniature pigs, which more closely mirror human metabolism and eating patterns, and found that injecting BRP prior to feeding reduced food intake over the next hour by up to 50% in both animals.
In separate experiments, obese mice treated with daily injections of BRP for 14 days lost an average of 3 grams – almost entirely fat – while control animals gained about 3 grams over the same period. The mice also had improved glucose and insulin tolerance.
There was no difference in the animals’ movements, water intake, anxiety-like behaviour, or faecal production.
Svensson has co-founded a company to launch clinical trials of the molecule in humans in the near future.
Before they can do that, the team needs to identify the receptors that bind BRP and solve its mechanism of action. They are also investigating how to help the peptide’s effects last longer in the body to allow a more convenient dosing schedule.
