On the weight scale: new technology will accelerate the creation of drugs for obesity and diabetes

Russian scientists have patented a technology that, according to them, will allow faster and more accurate testing of anti-obesity drugs, including semaglutide analogues, and other promising drugs. There is a high demand for such systems now, because the market for drugs acting as human intestinal hormones is growing rapidly, experts explained to Izvestia. However, it must be remembered that in general, such pharmaceutical support methods should be considered as temporary, with which it is easier to change the lifestyle and nutrition system. Without this, a long-term effect is impossible, the doctors concluded.

What are GLP-1 receptors?

Sirius University of Science and Technology has developed and patented a technology that allows faster and more accurate testing of potential drugs that affect GLP-1 (glucagon-like peptide-1) receptors. They are located on the surface of pancreatic cells and act as "signal receivers". After eating, the intestines produce a hormone that binds to these receptors and signals the cells to release insulin, thereby lowering blood sugar levels. Studies of such receptors help to create drugs that can more precisely regulate metabolism.

The development is a cell line, that is, a population of cells of the same type, the use of which can significantly accelerate the early stages of drug development and reduce the volume of animal experiments.

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Specialists have patented a technology for creating a stable cell line that expresses the GLP-1 receptor and the green fluorescent protein (GFP) with a single RNA. This solution makes it easier to monitor the condition of cells and the quality of experiments: scientists can quickly assess the stability of a cell population using a fluorescence microscope or other techniques, without performing complex analyses.

— Most existing systems use temporary expression to test GLP-1R agonists (a class of drugs that lower blood sugar levels) — researchers reinsert the receptor and reporter genes into cells each time. It takes a long time and increases the chance of errors. We have created a stable line that is always ready to work — screening becomes faster, more reliable and more reproducible," Alisa Krasnodubets, researcher at the Medical Biotechnology department at the Sirius University Translational Medicine Research Center, told Izvestia.

The created system is used in joint projects with pharmaceutical companies and academic laboratories for screening molecules. In addition, it is used to conduct tests for other receptors of the same family — GIPR (involved in the absorption of fats and additional stimulation of insulin) and GCGR (increases glucose levels when the body is hungry). They perceive the signal from the hormones of the same name and regulate the metabolism.

Due to this, the new cell line can be used as a universal platform for evaluating the activity of active compounds. The results of the work will speed up the early stages of drug development and reduce the volume of animal experiments, which meets modern ethical and scientific standards of preclinical research, the developers emphasized.

The demand for medicines for obesity and diabetes

The development is really promising, as it serves as a tool for early screening of GLP-1, GIP and GCGR receptor agonists, Albert Rizvanov, head of the Personalized Medicine Center of Excellence at Kazan (Volga Region) Federal University, told Izvestia. A stable cell line accelerates and reduces the cost of primary selection of compounds, which is important when searching for new semaglutide analogues with potentially milder therapeutic effects.

"There is indeed a high demand for such systems, because the market for drugs acting on GLP—1 receptors is growing rapidly, and developers need fast and reproducible laboratory models," the expert said.

The development falls into one of the most dynamic pharmaceutical segments: the global market of GLP-1 agonist drugs is estimated at more than $50 billion and is growing by 30-40% annually. Speeding up preclinical tests potentially reduces the time to market the drug by 6-12 months, which is critical in the context of the patent race, explained Maxim Kolyasnikov, associate professor at the UrFU Institute of Economics and Management and the Department of Future Technologies at MIPT.

— However, patent protection only in Russia significantly limits monetization: the leaders of the pharmacology market use their own patented screening platforms. Validation in comparative studies with industry standards and foreign solutions is needed to confirm competitiveness," he said.

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The therapeutic effect, as well as the undesirable effects of such drugs, is associated with a decrease in appetite and an acceleration of satiety from food. In conditions of a shortage of nutrients other than fat and water, a person loses muscle mass (up to 40% of the lost weight), and may also experience all the effects of prolonged starvation, including decreased thyroid function, decreased immunity, and more, a leading market expert at NTI Helsnet and the Union of Healthy Health told Izvestia. Andrey Martyushev is a good fit. This is especially dangerous if a person does not change their diet: they do not switch from fast food and "empty calories" to foods with high nutritional value.

— Therefore, such medications should be considered as temporary "crutches", with which it is easier to switch to optimal nutrition, — said the specialist. — The fact is that obesity is a consequence of excessive insulin production, followed by insulin resistance. And excess insulin, in turn, is a consequence of the signals that we give to the body by our behavior: diet and diet, factors of chronic inflammation and stress. The body obediently obeys our behavior. And no medicine can reverse these causal relationships.

Therefore, in the treatment of obesity, medicine can be only part of a system in which lifestyle correction, primarily nutrition, plays a leading role, the specialist noted.