New drug target identified for COPD
A research team led by the Centenary Institute and the University of Technology Sydney say they have identified a new drug target for the treatment and prevention of chronic obstructive pulmonary disease (COPD), an inflammatory lung disease that causes airway blockages and makes it difficult to breathe. Secreted by mast cells, a part of the immune system, the drug target is an enzyme known as mast cell chymase-1 (CMA1).
Dr Gang Liu, a researcher at the Centenary UTS Centre for Inflammation, said COPD is caused by cigarette smoke, air pollution, bushfire smoke and other particulate matter. “Over time,” he said, “the lungs breathe in toxic material and become inflamed. Lung function is subsequently impaired, leading to breathing difficulties which can then turn fatal.”
In their new study, published in the European Respiratory Journal, the researchers discovered elevated CMA1 levels in the lung tissues of patients with severe COPD. The CMA1 levels were approximately double that found in the lung tissue of mild-COPD patients and healthy individuals.
“CMA1 induces macrophages (a type of white blood cell) to release pro-inflammatory cytokines in the lung,” said Liu, who served as lead author on the study. “It’s this increased inflammation that can drive the development of COPD and poor outcomes for patients.”
Subsequent investigation of the equivalent CMA1 enzyme found in mice — an enzyme known as mMCP5 — confirmed the enzyme’s pivotal role in COPD. Liu said, “We were able to show in experimental COPD that inhibiting mMCP5 provided protection against inflammation and macrophage accumulation, harmful structural changes of the lung, emphysema and impaired lung function.”
Professor Phil Hansbro, the study’s senior author and Director of the Centenary UTS Centre for Inflammation, said the team’s research offers up a new therapeutic target to help combat COPD.
“There is currently no cure for COPD, and effective therapies to treat and manage the disease are urgently needed,” Hansbro said. “Our study suggests that developing new drugs to inhibit CMA1 and reduce cytokine inflammation may be a novel treatment for this devastating disease that affects so many lives.”
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