Novel Treatment Reverses Inflammatory Response in COPD Mouse Models

Inhibiting the receptor for advanced glycan end products (RAGE) has an essential protective role in chronic obstructive pulmonary disease (COPD), according to a study published in the Federation of American Societies for Experimental Biology.

Prior studies have identified RAGE as a susceptibility gene for COPD. However, little was known about the role RAGE played in the pathogenesis of COPD.

“RAGE disturbances in pulmonary disorders are precise and effective strategies with beneficial clinical effects,” said investigator Se-Ran Yang, DVM, PhD. “Blockade of RAGE as a novel clinical therapeutic for COPD ameliorates emphysema/COPD development and progression.”

The investigators sought to determine the molecular mechanism RAGE uses to influence COPD, by investigating the efficacy of the RAGE-specific antagonist FPS-ZM1 administration in in vivo and in vitro COPD mouse models.

First, the mice were injected with an in vivo COPD inducer and FPS-ZM1, followed by an assessment of the infiltrated inflammatory cells and their production of cytokines. The cellular expression of RAGE was determined in protein, serum, and bronchoalveolar lavage fluid in mice, as well as in the serum of human donors and patients with COPD, according to the study.

The investigators analyzed downstream damage-associated molecular pattern (DAMP) and danger signals in vivo and in vitro, and in patients with COPD.

The results of the study showed that the expression of membrane RAGE in initiating the inflammatory response, and of soluble RAGE acting as a decoy, were associated with the up-regulation of DAMP-related signaling pathways via Nrf2.

FPS-ZM1 administration significantly reversed emphysema in the lungs of mice, and significantly reduced lung inflammation in Nrf2 mice, according to the study.

“Our data indicate for the first time that RAGE inhibition has an essential protective role in COPD,” the authors wrote. “Our observation of RAGE inhibition provided novel insight into its potential as a therapeutic target in emphysema and COPD.”