The key to healthier weight loss drugs could be found somewhere unexpected: inside a python’s blood.
The slithering serpents have an appetite-suppressing compound in their blood that helps them consume large meals and also go months without food — while remaining metabolically healthy, researchers at the University of Colorado Boulder, Stanford Medicine and Baylor University announced this week.
The findings could help drugmakers to develop new medications that curb patients’ appetite without nausea and muscle loss, common side effects of popular drugs such as Ozempic and Wegovy.
Millions of Americans currently use the drugs, but about half stop using them during the first year due to side effects, cost, age and other factors.
Using this research, drugmakers could one day create chemically-made matches of the compound in pythons for improved drugs, the researchers said.
The research in pythons follows the discovery of a hormone in the Gila monster – a venomous lizard found in the U.S. and Mexico – that regulates blood sugar levels, the inspiration for Ozempic and Wegovy’s active ingredient semaglutide.
“This is a perfect example of nature-inspired biology,” Leslie Leinwand, a distinguished professor of molecular, cellular and developmental biology at Colorado University Boulder and a senior author of the research, said in a statement.
“You look at extraordinary animals that can do things that you and I and other mammals can’t do, and you try to harness that for therapeutic interventions,” she said.
“Obviously, we are not snakes,” said Dr. Jonathan Long, an associate professor of pathology at Stanford. “But maybe by studying these animals we can identify molecules or metabolic pathways that also affect human metabolism.”
Pythons have an extraordinary metabolism – one of the fastest of all animals – which speeds up to 4,000 times their normal level as the reptiles digest their prey.
After pythons eat, the researchers found that 208 metabolites – compounds produced when the body breaks down food – increased significantly, and that the compound called para-tyramine-O-sulfate increased by 1,000 times its regular amount.
By giving this metabolite, also known as “pTOS,” to obese or lean mice, the researchers found that it affected the appetite center of their brain, leading to weight loss without causing stomach issues, a decline in energy level or muscle loss.
After 28 days, the mice lost nine percent of their body weight, with no changes in the amount of water they drank.
The metabolite is already present in human urine at low levels and increases somewhat after we eat, but most of the research on pTOS to date has been in mice or rats.
Further study showed that the effect of pTOS is not due to changes in hormones, like current weight loss medications on the market.
Instead, the researchers found that pTOS is a byproduct of bacterial breakdown of amino acid called tyrosine, which is found in dietary protein. Treating the pythons with antibiotics before they ate totally erased their increase in pTOS levels.
“We’ve basically discovered an appetite suppressant that works in mice without some of the side-effects that GLP-1 drugs have,” said Leinwand.
The researchers also analyzed pTOS levels in humans using six publicly available datasets of blood from healthy volunteers that were collected before and after eating.
In five of the six datasets, pTOS levels were elevated, but only by a very small amount for most people. However, one person saw an increase around five times larger than the others.
The team also hopes to look into more of the python’s increasing metabolites, some of which rose by up to 800 percent.
“We’re not stopping with just this one metabolite,” said Leinwand. “There’s a lot more to be learned.”
Leinwand and her colleagues have created a start-up called Arkana Therapeutics to work toward commercializing their research.
She noted that the findings may also have the ability to help treat age-related muscle loss called sarcopenia. Sarcopenia affects approximately 10-20 percent of adults aged 60 and older, according to the Department of Health and Human Services.
There are no therapies to reverse or stop sarcopenia.
