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A revolutionary study published in Nature introduces a new obesity treatment that surpasses the weight loss results of current drugs in mice. This method involves delivering molecules directly to the brain’s appetite control center, influencing neuroplasticity.
A new weight-loss drug utilizes the hormone GLP-1 to target brain areas controlling appetite, potentially reducing side effects and improving effectiveness compared to existing drugs, with human trials pending.
“I consider the drugs available on the marked today as the first generation of weight-loss drugs. Now we have developed a new type of weight-loss drug that affects the plasticity of the brain and appears to be highly effective.”
So says Associate Professor and Group Leader Christoffer Clemmensen, from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, who is senior author of the new study, which has been published in the prestigious scientific journal Nature.
In the study, Christoffer Clemmensen and colleagues demonstrate a new use of the weight loss hormone GLP-1. GLP-1 can be used as a ‘Trojan Horse’ to smuggle a specific molecule into the brain of mice, where it successfully affects the plasticity of the brain and results in weight loss.
“The effect of GLP-1 combined with these molecules is very strong. In some cases, the mice lose twice as much weight as mice treated with GLP-1 only,” Christoffer Clemmensen explains.
This means that future patients can potentially achieve the same effect with a lower dosage. Moreover, the new drug may be an alternative to those who do not respond well to existing weight-loss drugs.
“Our studies in mice show side effects similar to those experienced by patients treated with the weight loss drugs available on the market today, including nausea. But because the drug is so effective, we may be able to lower the dosage and thus mitigate some of the side effects in the future – though we still don’t know how humans respond to the drug,” he says.
Testing of the new weight loss drug is still in the so-called preclinical phase, which is based on studies with cells and on experimental animals. The next step is clinical trials with human participants.
“We already know that GLP-1-based drugs can lead to weight loss. The molecule that we have attached to GLP-1 affects the so-called glutamatergic neurotransmitter system, and in fact, other studies with human participants suggest that this family of compounds has significant weight loss potential. What is interesting here is the effect we get when we combine these two compounds into a single drug,” Christoffer Clemmensen stresses.
The drug must undergo three phases of clinical trials on human participants. According to Christoffer Clemmensen, it can therefore take eight years before the drug could be available on the market.
The brain defends excessive body weight
Christoffer Clemmensen and colleagues developed an interest in molecules that are used to treat chronic depression and DOI: 10.1038/s41586-024-07419-8
Christoffer Clemmensen, along with postdoc Jonas Petersen and a former scientist from the University of Copenhagen (Anders Klein), have co-founded of the biotech company Ousia Pharma, which is a spinout company from the University of Copenhagen. The company is continuing to develop the medical concept presented in this study for the treatment of severe obesity.