Compound May Protect Against COPD-Related Lung Damage
FPR-ZM1 was seen to reverse the inflammatory response lung disease in mice.
The authors of a new study published by The FASEB Journal discovered a drug that may be effective in fighting chronic obstructive pulmonary disease (COPD), which can have life-threatening effects.
COPD is a broad term used to describe different progressive lung diseases, such as emphysema and chronic bronchitis. Patients with COPD typically experience shortness of breath, wheezing, or coughing. Currently, the only treatment options are limited to inhalers and inhaled or oral steroids to provide symptom control. These patients may also require pulmonary rehabilitation if the disease progresses.
Since lung damage from COPD cannot be reversed, preventing the damage from taking place is important. These findings suggest that a new treatment may protect the lungs from damage related to COPD through reversing the inflammatory response.
In the study, the investigators analyzed the efficacy of a receptor for advanced glycan end-products (RAGE)-specific antagonist chemical compound, FPR-ZM1.
The researchers found that FPR-ZM1 reversed inflammation and protected against COPD in mice.
"RAGE disturbances in pulmonary disorders are precise and effective strategies with beneficial clinical effects," said researcher Se-Ran Yang, DVM, PhD. "Blockade of RAGE as a novel clinical therapeutic for COPD ameliorates emphysema/COPD development and progression."
The researchers tested the compound in both in vivo and in vitro models of COPD to better determine how RAGE influences the disease, according to the study.
In mice, the investigators injected the animals with a COPD inducer and FPS-ZM1, and examined the invasion of inflammatory cells and the creation of cytokines.
The cellular expression of RAGE—inciting inflammatory response— and soluble RAGE—acting as a decoy—was examined in protein, serum, and bronchoalveolar lavage fluid in mice, according to the study. This was also observed in serum of human patients with COPD.
The authors then analyzed downstream damage-associated molecular patterns (DAMPs) and danger signals in cells, mice, and humans with COPD. They discovered that RAGE was linked to an up-regulation of DAMP-related signaling pathways via Nrf2, which is a regulator of the antioxidant system, according to the study.
The researchers also found that administering FPS-ZM1 reduced emphysematous lung symptoms in mice models of COPD.
While additional studies are needed to further confirm the findings, this may present patients with a treatment option to protect against COPD symptoms.
"No one expected the pathogenic roots of COPD to be simple, and this study gives us an indication of the complexity involved.," said Thoru Pederson, PhD, editor-in-chief of The FASEB Journal. "The current pharmacological armamentarium is limited, and studies like this are thus extremely valuable as a foundation."