Just one dose: Gene Therapy for Obesity Outperforms Semaglutide

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Just one dose: Gene Therapy for Obesity Outperforms Semaglutide

Just one dose: Gene Therapy for Obesity Outperforms Semaglutide, Research Shows.

In the past, individuals seeking rapid and significant weight loss had only one option: weight loss surgery.

However, the advent of GLP-1 class medication semaglutide offered a pharmaceutical means to achieve approximately 15% weight reduction.

Meanwhile, tirzepatide achieved a remarkable 22.5% weight loss in Phase 3 clinical trials, nearing the effectiveness of surgical interventions.

Yet, both of these GLP-1 class medications faced some challenges. They required weekly injections, and once discontinued, weight regain was likely to occur gradually.

This phenomenon is rooted in the biology of obesity, as the human brain seems to have a set point for how much fat the body should store, and medications could only mask this set point rather than fundamentally alter it.

The notion of maintaining weight loss after discontinuing medication didn’t align with the biology of the human body.

However, a company named Fractyl Health is developing a once-in-a-lifetime weight loss medication that aims to provide long-term obesity prevention with a single injection.

Recently, at the European Association for the Study of Diabetes (EASD) annual meeting, Fractyl Health released head-to-head experimental data between their GLP-1-based pancreatic gene therapy candidate, Rejuva® (GLP-1 PGTx), and semaglutide in a preclinical obesity mouse model.

The results demonstrated that in a high-fat diet-induced obese mouse model, a single administration of GLP-1 PGTx delivered via adenoviral-associated virus (AAV) led to a 24.8% overall weight reduction on the 15th day, while obese mice treated with semaglutide at a dose of 10 nmol/kg/day experienced an 18.4% overall weight reduction. This outcome provides further evidence for the potential of one-time administration of GLP-1 gene therapy to overcome the challenges faced by existing GLP-1 class medications in the treatment of type 2 diabetes and obesity.

On the 15th day of the study, neither the gene therapy group nor the semaglutide treatment group mice had reached a stable weight. Compared to the control group mice that continued for 15 days, both the semaglutide treatment group and the gene therapy group mice reduced their food intake, providing a mechanism for their weight loss.

Dr. Mark Kay, a professor at Stanford University School of Medicine and scientific advisor to Fractyl Health, stated that gene therapy has already shown success in some rare diseases, potentially opening doors for gene therapy’s ongoing benefits in more common conditions like obesity and type 2 diabetes. The efficacy of GLP-1 PGTx in a preclinical obesity mouse model and the accumulated toxicological research suggest that localized gene therapy in the pancreas may now be feasible, offering a solution to society’s most troubling chronic diseases.

Dr. Timothy Kieffer, Chief Scientific Officer of Fractyl Health, said, “Our goal is to design a better GLP-1 therapy that has the potential for improved weight loss, better tolerability, and longer-lasting effects. Our GLP-1 PGTx may offer these benefits as it targets the pancreas, aiming to mimic human physiology and potentially provide lasting benefits.”

Dr. Harith Rajagopalan, CEO of Fractyl Health, added, “The role of the GLP-1 mechanism in obesity and type 2 diabetes is evident, but we also know that what we need is a treatment for type 2 diabetes and obesity that remains effective even when patients stop taking the medication. Our goal with the Rejuva platform is to develop a candidate gene therapy that can durably alter the course of obesity and type 2 diabetes. The current preclinical concept validation data further solidifies the feasibility of this approach.”

Just one dose: Gene Therapy for Obesity Outperforms Semaglutide

In summary, by delivering the GLP-1 gene through adenoviral-associated virus (AAV) in a specific and one-time treatment, they achieved better weight loss results in diet-induced obese mouse models compared to long-term semaglutide use.

These preclinical research findings enhance the potential of GLP-1 class medications in the treatment of obesity, offering hope to overcome the challenges faced by existing GLP-1 class drugs. The company plans to advance this approach to clinical trials for human type 2 diabetes treatment in 2024.

It’s important to note that long-lasting weight loss medications don’t address the root causes of the obesity epidemic, as many individuals become obese due to a lack of access to healthy food or insufficient physical activity. However, for those who are already obese and seeking a swift escape from obesity, these new types of weight loss medications provide a promising option.

Pharmaceutical weight loss is not and will not be the sole solution, but their emergence represents a revolutionary step in our battle against the obesity epidemic.