Against cancer and obesity
According to a new study on mice conducted by Washington University School of Medicine in St. Louis, an experimental cancer drug that deprives tumors of their energy source also leads to the restoration of normal metabolism of the entire body.
The researchers used mice genetically prone to obesity, and mice with obesity due to a diet high in fat and sugar. The animals received an experimental antitumor drug pegylated arginine deiminase (pegylated arginine deiminase, ADI-PEG 20). Treatment with ADI-PEG 20 increased insulin sensitivity, normalized cholesterol levels, reduced the accumulation of lipids in the liver and reduced inflammation. Mice genetically prone to obesity were protected from weight gain by the drug, and mice that received food with a high fat and sugar content showed a decrease in body weight.
Histological sections of the liver of mice on a diet high in fat and sugar. On the left, the liver of an untreated mouse: there are a lot of white spots – fat cells. On the right, the liver of a mouse treated with ADI-PEG 20: there is less fat accumulation in the liver.
Currently, ADI-PEG 20 is being investigated for possible use as a treatment for a number of tumors, including sarcoma, breast and pancreatic cancer. The drug breaks down the amino acid arginine in the blood and deprives cancer cells of a key source of energy. Researchers became interested in studying ADI-PEG 20 after they discovered that the genes responsible for the breakdown of arginine are overly active when the body is in a state of starvation. They suggested that the drug could mimic this effect of fasting.
Indeed, the researchers found that ADI-PEG 20 triggers the process of autophagy in cells – a kind of cleaning at the cellular level. Cells undergoing autophagy burn their own cellular waste as fuel. During fasting, when there is no new fuel coming from the outside, the cells switch to autophagy to extract fuel from the inside.
Thus, ADI-PEG 20 appears to mimic some of the metabolic and therapeutic effects of fasting. In mice genetically prone to obesity, the average weight after treatment was about 25% less than in mice who did not receive the drug. And rodents fed with a high fat and sugar content experienced similar weight loss after treatment.
The drug ADI-PEG 20 has been tested in clinical studies examining its safety and efficacy in the treatment of several types of tumors, including breast, prostate, pancreatic and liver cancers. In general, metabolic therapy tends to have fewer side effects and is safer than chemotherapy, radiation therapy and even younger immunotherapy.
The research team plans to conduct a clinical trial to find out whether ADI-PEG 20 causes similar metabolic changes and weight loss in obese people and whether it is safe to take it for a long time. The drug is a protein, so there is a possibility that patients may develop an immune response to it over time.
Article by Y.Zhang et al. Pegylated arginine deiminase drives arginine turnover and systematic autophagy to dictate energy metabolism is published in the journal Cell Reports Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Washington University School of Medicine in St. Louis: Drug mimics beneficial effects of fasting in mice.