Blocking COPD Risk-factor Molecule Could Be Path to Treatment, Study Reports

Blocking a molecule that is a risk factor for chronic obstructive pulmonary disease (COPD) could be a path toward treating the disease, according to a study.

Researchers demonstrated that blocking a factor known as RAGE (receptor for advanced glycan end products) prevented inflammatory signaling and reduced airway damage in mice.

The study,  “Blockade of RAGE ameliorates elastase-induced emphysema development and progression via RAGE-DAMP signaling,” was published in The FASEB Journal.

Genetic studies have long identified RAGE as a risk gene for developing COPD. But whether it was  involved in the disease’s processes was unknown.

Researchers at Kangwon National University in Korea decided to study the mechanisms by which RAGE might contribute to COPD. As a first step, they examined how much of the molecule was present in the lungs and blood serum of mice and humans.

The molecule exists in both membrane-bound and soluble forms that are released from cells. Analyses showed that COPD patients and smokers who did not have COPD had higher levels of the membrane-bound form of the disease in their lungs than non-smoking healthy people. In contrast, patients and smokers had lower levels of soluble RAGE.

Analyses showed that blocking the molecule with a compound called FPS-ZM1 reduced lung emphysema and airway inflammation in mice with COPD. The treatment also reduced oxidative stress in the lungs. Oxidative stress is an imbalance between free radicals, which can damage cells, and the body’s anti-oxidant defense system, which fights free radicals.

Reduced inflammation occurred when the RAGE blocker prevented the activation of a pathway that becomes activated in response to tissue damage, researchers said. Although such inflammatory events have beneficial features, they become hazardous in a chronic disease like COPD.

Further experiments suggested that RAGE blocking affects only the inflammatory component of disease, and does not directly impact airway enlargement.

“RAGE disturbances in pulmonary disorders are precise and effective strategies with beneficial clinical effects,” Se-Ran Yang, PhD, the senior author of the study, said in a press release. He is an associate professor in the Kangwon School of Medicine’s Department of Thoracic and Cardiovascular Surgery.

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

Thoru Pederson, PhD, editor of The FASEB Journal, added that in COPD, the “current pharmacological armamentarium is limited, and studies like this are thus extremely valuable as a foundation.”