After screening 20,000 protein-encoding genes in the human body, Stanford researchers have identified a naturally occurring molecule that works like semaglutide, most popularly known as Ozempic, to put the brakes on appetite and weight gain.
Since its release in the United States in 2017, the injectable drug Ozempic has not only helped thousands lose weight, but it's also been shown to have a wide range of other health-boosting effects. It has shown promise in fighting alcohol addiction; relieving knee pain from osteoarthritis; reducing the risk of kidney failure and death in some type 2 diabetics; and temper the negative effects being overweight has on the heart.
Despite all its promise, however, Ozempic does come with a range of side effects. These can range from relatively mild symptoms like nausea, diarrhea and dizziness to more serious effects like gallbladder disease, hypoglycemia, and pancreatitis. The drug has even been linked to suicidal ideation and up to a sevenfold increase in a rare form of blindness known as an "eye stroke."
So, researchers led by a team at Stanford Medicine set out to see if they could find a natural alternative to semaglutide that would deliver its weight-loss benefits while reducing or eliminating its side effects. To do so, they focused on prohormones, biologically inert protein molecules that become active when they are chopped up into smaller parts called peptides by other protein molecules. Some of these peptides function as hormones in the body.
The researchers developed an algorithm called Peptide Predictor that analyzed thousands of genes that encode prohormones, and more specifically looked at the sites where each could be carved up by the action of outside proteins. This led them to find a small peptide named BRP which consists of only 12 amino acids yet increased the action of neuronal cells in the brain tenfold over controls. Developing a drug that only works in the brain, they reasoned, would be an improvement over Ozempic, which works throughout the whole body.
“The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas and other tissues,” said study co-author and assistant professor of pathology Katrin Svensson. "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.”
The researchers then conducted tests of BRP on both mice and minipigs, whose systems more closely mimic that of humans than rodents. They found that one injection of BRP reduced food intake in both species by up to 50% during the following four hours. In obese mice, a daily injection of BRP for 14 days caused the rodents to lose an average of three grams (about 0.1 oz) due primarily to fat loss, and to demonstrate better glucose and insulin tolerance.
They also did not see any side effects of BRP after observing the animals' water intake, fecal production, movements or behaviors that would be associated with anxiety.
Svensson has now co-founded a company with the intention of moving to human clinical trials of BRP, and she and her team are now studying ways to extend the duration of its effects in the body. This would make it easier to dose if it does prove to be an effective weight-loss solution for humans.
“The lack of effective drugs to treat obesity in humans has been a problem for decades,” Svensson said, speaking on the success of BRP in the animals. “Nothing we’ve tested before has compared to semaglutide’s ability to decrease appetite and body weight. We are very eager to learn if it is safe and effective in humans.”
The research has been published in the journal Nature.
Source: Stanford University
