A molecule produced in abundance by pythons following a large meal could hold the key to developing a new class of weight loss drugs with fewer side effects, according to a study published Thursday by researchers at the University of Colorado Boulder and two other institutions.
The researchers found the molecule, a metabolite called para-tyramine-O-sulphate or pTOS, acts on the hypothalamus, the brain’s hunger center. When obese mice were given frequent doses of pTOS, they ate less and lost weight, according to the study, which was published in the journal Nature Metabolism.
Leslie Leinwand, a professor of Molecular, Cellular and Developmental Biology at CU Boulder and the senior author on the study, said the discovery could lead to the development of weight loss drugs that don’t come with common side effects of the current class of GLP-1 medications. Those drugs can cause nausea and muscle loss.
“This is a perfect example of nature-inspired biology,” Leinwand 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.”
(Steve Peterson, special to The Colorado Sun)
Leinwand is already one of the most distinguished scientists working in Colorado. Two previous companies she cofounded based on research into certain types of heart disease each sold for billions of dollars to pharmaceutical companies. One of the therapies that work produced, a drug sold under the brand name Camzyos, has been used to treat more than 11,000 patients since it was approved in 2022.
The research on pTOS comes from a long-running side quest of hers to understand the incredible metabolic feats of pythons, which may go for months or more than a year without eating and then consume a meal equivalent to their entire body weight.
After that kind of meal, a python’s metabolism increases 4,000-fold and its heart expands 25% to pump all that nutrient-rich blood. Its pTOS levels spike 1,000-fold, according to the new study. Then, when the meal is fully metabolized, everything returns to normal with no damage to the heart and ample retention of muscle mass during the ensuing fast.
For the new study, Leinwand worked with Stanford University professor Jonathan Long, who specializes in research on chemicals in the blood related to energy consumption and expenditure. Previous research of his has looked at racehorses.
“If we truly want to understand metabolism, we need to go beyond looking at mice and people and look at the greatest metabolic extremes nature has to offer,” Long said in a statement.
Leinwand also worked with researchers at Baylor University in Texas, who conducted studies showing that mice dosed with pTOS — which is also found naturally in humans — ate less.
Leinwand, Long and two other CU researchers have now formed a company called Arkana Therapeutics to develop the discoveries into commercially available drugs. The company last year received a $127,500 grant to fund its work. Leinwand’s previous success in developing therapies means she also has contacts for venture capital firms that could also invest.
Leinwand and her colleagues envision creating synthetic versions of pTOS and other possibly beneficial metabolites found in pythons to treat obesity and other health conditions.
“We’re not stopping with just this one metabolite,” she said in a statement. “There’s a lot more to be learned.”