A whole new generation of weight loss treatments have transformed obesity treatment, helping people lose weight to levels that were previously thought difficult to achieve without surgery.
Injections such as Ozempic, Vegovy, and Monzaro mimic a hormone called GLP-1 that works to suppress appetite in different parts of the body.
Although their effectiveness in helping people lose weight has made them blockbusters, these drugs have also been linked to side effects such as nausea, vomiting, diarrhea, stomach pain, and constipation in some patients.
BRP, a 12-amino-acid appetite-suppressing molecule discovered by a team at Stanford Medicine in California, may help achieve weight loss effects with fewer side effects. It works primarily in the part of the brain that controls appetite, known as the hypothalamus.
How does BRP appear to be different?
Giles Yeo, professor of molecular neuroendocrinology at the UK Medical Research Council’s Metabolic Disease Unit, told DW that, because of the blood-brain barrier, only two parts of the brain sense the transmission of hormones — the hypothalamus and the hindbrain.
“Ozempic and all these gut hormones exert their primary effects through the back part of the brain,” he said.
“The hypothalamus is the hunger sensor. It’s responsible for everything from dealing with hunger to not being hungry. It’s trying to figure out within your body. Am I starving or not? How hungry am I?”
“The hindbrain does something different. It targets the visceral effect. It targets fullness, being uncomfortably full: ‘Oh my God – I’m full from Christmas! I’m so full, I feel like vomiting.'”
Current weight loss vaccines affect the hypothalamus, but they mostly target the hindbrain – and this produces feelings of fullness. “The problem with targeting here is that it has side effects such as nausea,” Yeo said. “In other words, the big side effect of these Ozempic-type drugs is nausea because it affects that part of the brain.”
BRP appears to act on a different pathway, affecting only the hypothalamus. This may cause fewer unpleasant side effects. Another potential benefit of BRP is that in animal tests with the compound, rats appeared to lose fat, but not muscle – another potential side effect of GLP-1 mimics.
‘Breathtaking’ discovery for peptide
BRP may prove to be a huge success, but the way it was discovered was unprecedented. In search of alternatives to GLP-1 mimics, Stanford researchers created an AI tool called Peptide Predictor that scanned nearly 20,000 human genes. It identified 2,683 potential hormone-like peptides – short chains of amino acids. He further reduced the number of candidates and tested about a hundred of them.
BRP was the winner. Daily injections of the peptide into obese mice caused them to lose weight, while untreated animals gained weight.
Professor Randy J. HK Ransom Professor of Surgery at the University of Michigan in the US. “The courage of sorting through huge numbers of peptides is truly breathtaking,” Seely said. “I’m amazed by the work.”
How likely is a human BRP drug?
Katrin Svensson, senior author of the study, has co-founded a company that plans to begin human clinical trials in the near future. But Seely says it is difficult to predict whether success in animal testing will translate to humans.
“The hardest thing to know is whether a drug based on this will have enough safety to become an approved obesity therapeutic,” he said. “Obesity is a chronic condition that needs to be treated over a long period of time. This means that such drugs need to be safe enough for people to use them for a long time.”
GLP-1-type drugs themselves are adapted versions of a natural hormone – the modification makes them last longer in the body. BRP can also be changed in a similar manner.
Even if the compound makes it through the necessary clinical human trials, GLP-1 mimics will still have clinical value because they have benefits beyond weight loss. For example, they may reduce cardiovascular risk. But BRP would offer a valuable alternative amid the growing crisis.
“The more tools we have to help people lose weight, the more people are likely to find their personal blend,” Yeo said. “If you’re more likely to stay on the medication, you’re more likely to stay at weight.”
“One billion people in the world are obese and now more people in the world die from obesity than die from actual famine,” he said. “This is the first time in human evolution that we’ve really reached this stage. And the more tools we have for treating obesity, the better.”