A new and promising therapy for obesity is being described in a groundbreaking article. This approach has been found to result in greater weight loss in mice compared to existing medications. The method involves transporting molecules into the brain’s appetite center and impacting the brain’s neuroplasticity.
Associate Professor and Group Leader Christoffer Clemmensen from the Novo Nordisk Foundation Center stated, “I consider the drugs available on the market 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.”The senior author of the new study is from the University of Copenhagen’s Basic Metabolic Research. The study, published in the scientific journal Nature, demonstrates a new use for the weight loss hormone GLP-1. The researchers used GLP-1 as a ‘Trojan Horse’ to smuggle a specific molecule into the brains of mice. This successfully affected the brain’s plasticity and resulted in weight loss. According to Christoffer Clemmensen, the effect of GLP-1 combined with these molecules is very strong, with some mice losing twice as much weight as those treated with GLP-1 alone.ns.
This indicates that future patients may potentially achieve the same result with a lower amount. Additionally, the new medication could be an option for individuals who do not respond well to current weight-loss medications.
“Our research in mice reveals side effects that are similar to those experienced by patients using the weight loss drugs currently available, such as nausea. However, due to the drug’s high effectiveness, we may be able to reduce the dosage and therefore alleviate some of the side effects in the future — although we are still uncertain about how humans will react to the drug,” he explains.
Testing of the new weight loss medication is still ongoing.The drug must undergo a process called the preclinical phase, which involves studies using cells and experimental animals. The next stage is clinical trials with human participants.
“We already know that drugs based on GLP-1 can result in weight loss. The molecule we have attached to GLP-1 affects the glutamatergic neurotransmitter system. Other studies with human participants suggest that this group of compounds has significant potential for weight loss. What is particularly interesting is the effect we see when we combine these two compounds into a single drug,” emphasized Christoffer Clemmensen.The process of clinical trials on human participants involves three phases, which can take up to eight years to complete before a drug can be available on the market, according to Christoffer Clemmensen. Clemmensen and colleagues focused on molecules used to treat chronic depression and Alzheimer’s disease, which block the NMDA receptor, a key player in long-term changes in brain connections related to learning and memory. Targeting these receptors with drugs can strengthen the brain’s defense against excessive body weight.
It is possible for these molecules to alter or weaken specific nerve connections.
“These molecules can cause lasting changes in the brain. Research has shown that even occasional treatment can result in long-term changes to brain function. In our research, we have observed molecular signs of neuroplasticity, particularly in the context of weight loss,” he says.
The human body has evolved to maintain a certain body weight and fat mass. From an evolutionary perspective, this has likely been beneficial as it has allowed us to survive periods of food scarcity. Today, food scarcity is not as common, but our bodies still retain this protective mechanism.Obesity is a widespread issue in many parts of the world, with a growing number of people dealing with this problem. According to Christoffer Clemmensen, “Today, more than one billion people worldwide have a BMI of 30 or more. This makes it increasingly relevant to develop drugs to aid this disease, and which can help the organism to sustain a lower weight. This topic is something we invest a lot of energy in researching.”
A method being explored involves using a Trojan Horse to carry small molecule modulators of neuroplasticity into appetite-regulating neurons. It is known that drugs based on the intestinal hormone GLP-1 effectively target this area.The key to weight loss lies in the brain’s appetite control center. This new drug works on a cellular level by combining GLP-1 and molecules that block the NMDA receptor. It uses GLP-1 to transport small molecules directly to the neurons that control appetite, preventing them from affecting the entire brain. This targeted approach is a breakthrough in weight loss medication. The chemist, Jonas Petersen, who synthesized the molecules, explains the significance of this new drug in combating obesity.tested a new approach using the GLP-1 peptide to target the appetite control center in the brain. This method allows us to deliver non-specific substances to this specific region of the brain. Many drugs struggle to cross the blood-brain barrier, making it difficult to treat brain disorders. However, small molecules like the GLP-1 peptide have easy access to the entire brain. This could be a promising strategy for treating difficult neurobiological conditions with fewer side effects.”The main focus is on obesity and weight loss, but this actually represents a completely innovative approach to delivering medications to specific areas of the brain. Therefore, I hope that our research can open the door to a completely new category of drugs for treating conditions such as neurodegenerative diseases or psychiatric disorders.”
What exactly is neuroplasticity?
Neuroplasticity, also known as brain plasticity, refers to the brain’s ability to restructure itself by forming new neural connections. This capability enables the brain to adapt to new experiences, acquire new skills, process new information, and recover from injuries.
Neuroplasticity exists in sSeveral levels of the nervous system can undergo various changes, from small alterations in individual neurons to significant transformations such as the formation of new neural connections or reorganization of brain areas. Christoffer Clemmensen, along with postdoc Jonas Petersen and former University of Copenhagen scientist Anders Klein, have co-founded Ousia Pharma, a biotech company that is a spinout from the University of Copenhagen. The company is working on further developing the medical concept discussed in this study for treating severe obesity.
