Updated:
Keep
The immune system deteriorates with age, making Covid-19 particularly deadly in older people, but to date, no clinically available medicine addresses this key risk factor.
A study published today in “Nature” shows that an oral drug that reverses multiple aspects of immune aging effectively prevents death in a mouse model of Covid-19, suggesting that the drug could be used to protect elderly patients. who are most at risk in the pandemic.
In the study, daily doses of BGE-175 (asapiprant) protected elderly mice from a lethal dose of SARS-CoV-2, the virus that causes Covid-19. 90% of the mice that received the drug survived, while all the untreated control mice died.
Treatment with BGE-175 was started two days after infection, when the mice were already sick, a period of time relevant to real-life clinical situations where patients would receive medication only after becoming symptomatic.
The model mouse used in the study closely mirrored the pathological progression of human Covid-19. The mouse-adapted strain of SARS-CoV-2 generated by the researchers caused a disease that shared many of the characteristics of human Covid-19: accumulation of fluid in the air sacs of the lungs, extensive infiltration of lung tissue by immune cells, and high levels of pro-inflammatory factors called cytokines.
BGE-175 is currently in a phase 2 clinical trial to test whether it can prevent disease progression and mortality in hospitalized older patients with Covid-19 and is being clinically developed by BioAge Labs.
“The Covid-19 pandemic has devastated older populations around the world,” says Kristen Fortney, PhD, executive director of BioAge and author of the study. “The promising preclinical data in this article show that BGE-175 almost completely protects aged mice from lethality in a convincing model of human Covid-19.
By reversing age-related declines in critical immune mechanisms, BGE-175 could allow older patients fight this disease more effectively.”
As we age, a biochemical pathway involving the signaling molecule PGD2 becomes more active, affecting immunity in two main ways: First, antigen-presenting cells called dendritic cells migrate less efficiently, slowing antibody responses and adaptive T cells.
Second, white blood cells called neutrophils infiltrate infected tissues more aggressively, which causes harmful inflammation. Therefore, the aging immune system is slower to respond to new infections and more likely to overreact once it mounts a response.
BGE-175 inhibits this pathway by blocking the interaction between PGD2 and its receptor, a protein called DP1. AI-based drug discovery platform BioAge identified the PGD2-DP1 pathway as a key target for immune aging.
As with the drug-treated animals, the genetically modified mice that failed to synthesize PGD2 or lacked DP1 had lower viral loads, exhibited less inflammation and tissue damage, and were less susceptible to death from viral infection, confirming that BGE-175 acts through the PGD2 pathway.
“Our findings clearly show that the therapeutic target of BGE-175 plays a key role in making the aging lung environment conducive to optimal immune function and thus counteracting immune aging,” said Stanley Perlman, author of the paper. of Nature. “The protective effect of the drug in mice supports the idea that BGE-175 corrects age-related decline in immunity, providing a strong justification to perform tests on older patients who are hospitalized with Covid-19”
A phase 2 clinical trial, launched in March 2021, is testing whether BGE-175 can prevent respiratory failure and mortality in older patients hospitalized with Covid-19. Because some cases of Covid-19 are associated with uncontrolled inflammation, which increases the severity and morbidity of the disease, the trial will also measure the effect of BGE-175 on the levels of inflammatory markersproviding information about BGE.
Because BGE-175 targets the host’s immune system rather than the invading virus, it has the potential to retain its effectiveness against emerging strains that may resist antiviral drugs or evade vaccine-based immunity. Similarly, since its mechanism of action is not specific to Covid-19, the drug could help older patients fight other viruses.
Pending positive results in the Phase 2 trial, BioAge intends to pursue broad clinical applications for BGE-175, including diseases such as influenza and pneumonia.
See them
comments