A drug prevents death from covid-19 in aging mice

Madrid, 21 Mar An oral drug directed against immune system deficiencies due to age protects aging mice from death by covid-19, according to the results published today in the journal Nature. 90% of mice receiving daily doses of the drug, called BGE-175 (asapripant), survived infection with a lethal dose of SARS-CoV-2, while all untreated rodents in the control group died. The drug is targeted against inflammation associated with immune aging rather than against viruses, so it has potential for use in the treatment of other infections that harm older people the most. The study is led by the University of Iowa (United States) and has the participation of the team led by Luis Enjuanes, at the National Center for Biotechnology (CNB-CSIC) in Spain. In both humans and animals, immune function decreases with age, which increases the severity of covid-19 in people over 65 years of age. The drug being studied reverses multiple aspects of immune aging and effectively prevents death in a mouse model of covid-19, suggesting that it could be used to protect elderly patients who are most at risk in the pandemic, the Bioage Labs laboratory notes in a statement. The mouse model reflected the progression of human covid-19, and the animal-adapted strain of SARS-CoV-2 caused a disease that shared many of the distinctive features with which it affects people, such as fluid accumulation in the air sacs of the lungs and high levels of pro-inflammatory factors called cytokines. Since BGE-175 targets the host's immune system and not the invading virus, it has the potential to maintain its effectiveness against emerging strains that may resist antiviral drugs or evade vaccine-based immunity, the note adds. In addition, it is being studied whether the drug could help older patients fight other viruses. The Spanish team has contributed to the research with a tool generated by them, the infective cDNA, an infective clone that allows the virus genome to be converted into DNA so that it can be manipulated in the laboratory, explains virologist Isabel Sola, who is also a signatory of the study, to Efe. The article aims to demonstrate that having an animal model such as mice “there is a greater possibility” of studying the mechanisms by which the virus causes damage, identifying possible causes and looking for more specific drugs, adds the virologist. The pathology of this virus, he emphasizes, “is, to a large extent, in the exaggerated inflammation it causes and the study shows that among all the mediators of inflammation that may be altered there are some that increase with age, which has allowed the identification of more specific drugs to expand the therapeutic arsenal”. The drug works by inhibiting the PGD2 protein DP1, which the team has identified as a key target for immune aging. Through this pathway, BGE-175 boosts dendritic cells that help the body identify pathogens and decreases neutrophil infiltration, which leads to harmful inflammation, thus combating the decrease in immunity that makes older people more vulnerable to infection. A phase 2 clinical trial is currently being conducted, in Argentina, Brazil and the United States, to test the potential of this drug to reduce mortality in elderly patients hospitalized by covid-19. CHIEF cr/acm