Obesity treatment researcher receives Lasker Award

scientist Joel Habener, Svetlana Modisovand Lotte Bjerre Knudsen The winners are 2024 Lasker Award GLP-1-Based Discovery and Development A revolutionary treatment for obesity and diabetes New medicine.

Recently, a drug developed from their research has helped to reduce addiction. Alzheimer's disease.

The Lasker Award for Clinical Medical Research recognized both Drs. Habener (Massachusetts General Hospital) and Moysof (Rockefeller University). Physiologically active forms of hormones (GLP-1) Knudsen (Novo Nordisk) was credited with turning it into a drug. Promotes weight loss.

Obesity in general As Failure of willpower, But for many people, diet and exercise don’t solve the problem. Historically, Attempts to make safe and effective medicines “Products to help people lose weight have not lived up to expectations,” the Lasker Foundation said in explaining this year's winners.

The road to a new era of weight management

In the 1970s, newly trained endocrinologist Joel Habener established a laboratory at Massachusetts General Hospital where he became interested in research. Diabetes.

Normally, glucose stimulates the pancreas to release insulin, which moves the sugar out of the bloodstream and into cells. Diabetes, Without insulin, blood sugar levels remain high, but cells lack insulin. According to the Lasker Foundation scientists' approach to research, while insulin therapy is one approach, researchers were exploring alternative tactics.

One such idea is Glucagon, a pancreatic hormone It was thought to be beneficial for diabetics because it increases blood sugar levels.

Habener used molecular biology to isolate the gene that codes for glucagon, but genetic manipulation of mammals was not permitted, so Anglerfish have a special organ that produces large amounts of glucagon..

active Peptide hormones are released from larger proteins The Lasker Foundation recalls that glucagon is produced by an enzyme that cleaves at a specific site. In 1982, Habener reported that the anglerfish glucagon gene encoded a predicted precursor protein that contained glucagon and a second peptide that was also similar to glucagon.

The same pair of amino acids, lysine and arginine, characterize the cleavage sites in several hormone precursor proteins, and cleavage at these sites releases both glucagon and a second peptide, the organization explains.

“A year later, Graham Bell (at Chiron) discovered that the gene encoding hamster glucagon also encoded a version of a second anglerfish peptide, which he named glucagon-like peptide 1 (GLP-1),” the Lasker Foundation adds.

Meanwhile, biochemist Svetlana Moysov, a researcher at Rockefeller University, identified the amino acid sequence that makes up the biologically active form of GLP-1. This active form can stimulate insulin release in the pancreas of rats.This is an important step towards developing a treatment for humans. Nature.

Following these important discoveries about GLP-1, the next step is Make it a medicineHowever, the hormone was quickly metabolized and lasted in the bloodstream for only a few minutes.

This is where Knudsen's work came in, Science recalls: A researcher at the Danish pharmaceutical company Novo Nordisk, Knudsen and her team realized that regular GLP-1 didn't work as a drug.

Instead, they developed a way to modify GLP-1 by attaching fatty acids to it, allowing the molecule to remain active in the body for longer before being broken down.

This study The first long-acting GLP-1-based drugLiraglutide was approved by the U.S. Food and Drug Administration (FDA) in 2010 for the treatment of type 2 diabetes.

“Today, newer variants such as semaglutide and tirzepatide, marketed as Wegovy and Zepbound, are key to treating obesity.” Nature Note.

How do these drugs work?

GLP-1 Reduce appetite and weightArmed with this knowledge, Knudsen and her team continued to study liraglutide and its effects, the Lasker Foundation notes. In a key study, non-diabetic obese or overweight participants lost an average of 11.5 pounds over a one-year period.

More than a third of participants who received liraglutide lost at least 5% of their body weight, and almost a quarter lost more than 10%. Feeling full and reducing hungerThis will encourage them to eat less voluntarily.

To further enhance its effectiveness, the researchers conducted nearly 4,000 trials to find the right combination of fatty acids and chemical bonds. SemaglutideKnown by the brand name Ozempic, the drug is a special diabetes treatment that lasts for up to 165 hours.

Liraglutide and semaglutide have now paved the way for second-generation drugs such as tirzepatide, which, unlike GLP-1's predominant pancreatic effect in diabetes treatment, Appetite suppression activity is concentrated in the brainResearchers, including Knudsen, are actively studying their behavior in the region.

Researchers are exploring the application of these drugs to a wide range of diseases. Chronic kidney disease, fatty liver disease, neurodegenerative diseases, etc. “GLP-1-based therapies are also effective in preventing cardiovascular diseases, including Alzheimer's, Parkinson's and addiction. Earlier this year, the FDA approved semaglutide to reduce heart attacks and strokes in people who are overweight or obese and have cardiovascular disease,” the award organization added.

Because of obesity, not for aesthetic reasons

In an interview AFPAward-winning researcher Svetlana Moysov says drugs like Ozempic: Liraglutide, and Tirzepatide It focuses primarily on diabetes.

“The real success is being able to treat obesity, and we should stick to that. I believe obesity drugs should never be used. for Cosmetic reasons,“I don't think there are any miracle drugs,” Moysov told AFP. medicine “There are side effects, and we know that when obese patients lose weight, they lose muscle mass, which is a serious problem, but it breaks new ground,” she added.

These medications should not be prescribed to everyone but should be considered part of personalized medicine, and it is important to understand their contraindications.

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