Fight Aging!

There are many potential approaches to interfere in the sweeping age-related chances to immune function. Of these, many stem from epigenetic changes characteristic of age, causing dysregulation via too much or too little production of a given protein, rather than more structural issues relating to reduced production of immune cells and increasing wear and tear of populations of immune cells lacking reinforcements. In this arena, a more efficient small molecule drug discovery process can allow for incremental improvement in immune function, assuming one can find a single point of intervention that has a high yield outcome in one or more populations of immune cells.

As we age, a biochemical pathway involving the signaling molecule PGD2 becomes more active, impairing immunity in two major ways: First, antigen-presenting cells called dendritic cells migrate less efficiently, slowing the adaptive T-cell and antibody responses. Second, white blood cells called neutrophils infiltrate infected tissues more aggressively, leading to damaging inflammation. Thus, the aged immune system is both slower to respond to new infections and more likely to overreact once it does mount a response. Bioage's drug BGE-175 inhibits this pathway by blocking the interaction between PGD2 and its receptor, a protein called DP1.

In the study, daily doses of BGE-175 protected aged mice from a lethal dose of SARS-CoV-2, the virus that causes COVID-19. Ninety percent of mice that received the drug survived, whereas all untreated control mice died. BGE-175 treatment was initiated two days after infection, when the mice were already ill, a time-frame relevant to real-life clinical situations in which patients would receive medication only after becoming symptomatic.

BGE-175 is currently in a Phase 2 clinical trial to test whether it can prevent disease progression and mortality in older patients hospitalized with COVID-19. "The promising preclinical data in this paper show that BGE-175 almost completely protects aged mice from lethality in a compelling model of human COVID-19. By reversing age-related declines in critical immune mechanisms, BGE-175 could allow older patients to more effectively fight off this disease."

Link: https://www.eurekalert.org/news-releases/946865