Brain-hacking weight-loss drug works even after you stop taking it

Brain-hacking weight-loss drug works even after you stop taking it
The 2.0 weight-loss drugs will target the brain's plasticity
The 2.0 weight-loss drugs will target the brain's plasticity
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The 2.0 weight-loss drugs will target the brain's plasticity
The 2.0 weight-loss drugs will target the brain's plasticity

The current breakthrough weight-loss drugs are only the beginning, according to Danish researchers hard at work on a new treatment that targets the brain's natural plasticity, which could offset bad side effects and provide more long-term benefits.

“I consider the drugs available on the market today as the first generation of weight-loss drugs," said Christoffer Clemmensen, Associate Professor at the Novo Nordisk Foundation Center for Basic Metabolic Research, at the University of Copenhagen, and senior author of the study. "Now we have developed a new type of weight-loss drug that affects the plasticity of the brain and appears to be highly effective.”

Where current GLP-1 drugs mimic the natural hormonal response following eating, signaling 'fullness' and slowing the emptying of the stomach, the new treatment instead uses GLP-1 peptide to "smuggle" molecules across the blood-brain barrier and into the appetite control center, to then block the NMDA receptor protein. This receptor has previously gained interest among researchers for its ability to aid in changing up brain connections to aid learning and memory. And unlike what's currently on the market, this new approach could harness the brain's plasticity to cement new pathways in its appetite center – pathways that would remain in place long after treatment had ceased.

“What is spectacular – on a cellular level – about this new drug is the fact that it combines GLP-1 and molecules that block the NMDA receptor," said researcher Jonas Petersen, the study's first author and the chemist who synthesized the molecules. "It exploits GLP-1 as a Trojan Horse to smuggle these small molecules exclusively into the neurons that affect appetite control. Without GLP-1, the molecules that target the NMDA receptor would affect the entire brain and thus be non-specific.”

It still has a GLP-1 backbone, but it's an entirely new approach requiring a much smaller dose and potentially stamps out the unpleasant side-effects that many experience while taking GLP-1 agonists like semaglutide and tirzepatide. And, given the current cost and invasiveness of frequent treatment needed to keep the weight off, this drug could offer long-term benefits, with intermittent doses enough to maintain its effectiveness.

“This family of molecules can have a permanent effect on the brain," said Clemmensen. "Studies have demonstrated that even a relative infrequent treatment can lead to persistent changes to the brain pathologies. We also see molecular signatures of neuroplasticity in our work, but in this case in the context of weight loss."

The catch? It's still at the stage of helping obese mice lose weight. But in these pre-clinical trials, it's far outperforming what's on the market now and is expected to move to tests on humans.

“The effect of GLP-1 combined with these molecules is very strong," Clemmensen said. "In some cases, the mice lose twice as much weight as mice treated with GLP-1 only.

"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," he added. "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."

The researchers note that while this study is focused on obesity, this drug-delivery system has potential to offer similar site-specific treatment for conditions such as neurodegenerative diseases or psychiatric disorders.

Meanwhile, last week the Danish pharmaceutical powerhouse Novo Nordisk, which brought Ozempic into the spotlight, announced it would soon begin a human trial using the GLP-1 agonist drugs as a potential treatment for alcohol use and liver damage. They're already being considered as a new treatment for Alzheimer's disease.

The current study was published in the journal Nature.

Source: University of Copenhagen

I'm a bit worried by 'pathways remaining after treatment ends'. Would you become anorexic?
Cymon Curcumin

I’m no expert but I don’t think it would. Anorexia isn’t fundamentally based on appetite or feeling full or not but rather on factors like perception of one’s weight. The worst that might be an issue would be a reduced appetite and even if that was permanent it is likely a lot easier to treat than obesity. Stimulating an appetite is a lot more natural and easier than suppressing.
Expanded Viewpoint
Does the cost of getting the various forms of cancer and other health issues from these poisons outweigh the cost of being over weight? If it does, then why do it?
Sounds like an exciting advance in this field.
Still, I when hear Danish, I salivate.
I hesitated to take these new drugs and it turns out they can be unpleasant, so I'm glad to see the tech moving forward to one day I can lose those stubborn 20 or 30 pounds that would put me in a healthier weight, especially as I get older...
This is pretty exciting...but the cost would need to be low enough for people to actually afford it. And, of course, if they haven't even started human trials it will be quite a while before it comes to market. Someone below asked if taking these "poisons" was worth the risk of cancers, etc. Is there evidence that they cause that (I'm assuming this person is referring to the current drugs). When you consider the effects of diabetes, heart disease, kidney disease, and inflammatory conditions I would say (depending on the risk level) that they ARE worth it. I've used the compounded semaglutide and it's been a total life changer for me. I stay to a really low dose because it's all I need, so I have zero side effects and I actually haven't lost a lot of weight, but I have had diabetes for 20 yrs and this is the first time my A1c has been below 7 in all that time. It has changed my relationship to food and I no longer have any cravings. But the most exciting thing for me has been that it has apparnently had a dramatic effect on inflammation in my body overall...I've had psoriatic arthritis (which is inflammatory) and since about a week after starting the semaglutide I have had ZERO pain or swelling in my foot and ankle (which had been constant for over 15 yrs now even though I've been on Otezla for years). It's the first time I've had no joint or lower back pain for many many years. They don't talk about the effects of semaglutide on inflammation nearly as much as they should because it's a true miracle.