Low dose of experimental cancer drug cuts appetite to target obesity
Through experiments involving a drug originally developed to suppress the growth of tumors, scientists have happened upon a potential new anti-obesity treatment, demonstrating it can trigger weight loss in mice. The promising oral therapy works by activating a key hunger-suppression pathway, which resulted in the treated animals consuming significantly less food over the course of a month.
Camptothecin is a promising experimental cancer drug known to inhibit a certain DNA repair enzyme and therefore has potential to suppress tumor growth. The authors of this new study, from China's Northwest A&F University, were drawn to the drug after discovering it has useful effects on a hormone called growth differentiation factor 15 (GDF15).
This hormone is known to circulate through the body in response to different stimuli, such as stress. Research has also shown that elevated levels of it lead to a reduction in body weight, and when it is suppressed obesity can result. This led the scientists to search for drugs that can boost its production, working their way through a database of gene expression profiles of human cells responding to different drugs.
This database, called the "Connectivity Map," showed that when cells are exposed to camptothecin, their expression of GDF15 is elevated. So, the team orally administered obese mice with the drug, which did indeed rapidly increase levels of GDF15 in their blood. Over the course of 30 days, these mice reduced their food consumption by around 12 percent, and their body weight by around 11 percent. When administered to lean mice, the scientists observed none of these effects, with GDF15 levels remaining unchanged.
While camptothecin has been investigated as an anti-cancer treatment, trials have hit roadblocks due to safety concerns over its use in humans. Critically, the dosage used in this study equates to around one-thirtieth of the lowest dose used in human anti-cancer trials.
Moreover, the drug appears to work via a separate mechanism in tackling obesity, with the team demonstrating its isolated effects on the GDF15 pathway by targeting the hormone with antibodies and by knocking down the related gene expression, which prevented its weight loss effects.
Its safety as a potential weight-loss treatment is therefore yet to be determined, but the early results are promising.
"We believe our results convincingly argue that camptothecin may have therapeutic benefits for obesity and its associated metabolic disorders," said study leader Jiang Wei Wu. "Further study is needed to evaluate its efficacy and safety in advanced models to increase the translational impact."
The research was published in the journal PLOS Biology.