Chronic obstructive pulmonary disease (COPD) is one of the most common and deadly diseases worldwide. Until now, COPD was not curable.
In a new study, researchers have now succeeded in curing COPD in mice exposed to chronic cigarette smoke.
Their goal is to test the novel therapeutic approach in human clinical trials over the next few years.
The research was conducted by a team at Helmholtz Zentrum München and at the German Cancer Research Center (DKFZ).
More than 250 million people suffer from COPD, a progressive inflammatory lung disease. On the list of the most frequent causes of death worldwide, COPD ranks third behind heart attacks and stroke.
The primary cause of COPD is exposure to cigarette smoke. Ninety percent of COPD patients are or have been chronic smokers. Other risk factors include exposure to air pollution.
Despite intensive research efforts, there is no cure for COPD. Resulting fibrosis and lung epithelial cell death are key features of COPD, preventing patients from breathing effectively.
Current therapies focus on relieving symptoms (mainly breathlessness and cough with phlegm) and reducing the progression of the disease and its comorbidities (mainly muscle wasting).
In severe cases, patients are in need of lung transplantation.
One of the biggest issues in COPD is that the lung cannot regenerate itself.
Therefore, a treatment that cures the disease needs to focus on lung tissue regeneration and blocking of lung epithelial cell death.
In 2009, the team prevented liver tissue from chronic inflammation and fibrosis. The development of diseases in the liver and the lung show many similarities.
In COPD, immune cells form newly organized structures in the lung, so-called tertiary follicles, which are known to play an important role in the disease progression.
The formation of these follicles requires the activation of the lymphotoxin beta receptor in the lung—the same receptor which was targeted in Heikenwälder’s study in the liver.
The researchers therefore blocked the signaling of the lymphotoxin beta receptor in the lungs of mice which had developed smoke-induced COPD typical immune cell follicles, fibrosis, and lung epithelial cell death.
The researchers found that the regeneration of compromised lung epithelial cells is induced by so-called Wnt signaling which is automatically activated through the blocking of lymphotoxin beta receptor signaling in those cells.
In previous experiments, re-activation of Wnt signaling in mice has been proven to induce lung repair.
The team says this could become a novel therapeutic approach for COPD. The idea is to develop lymphotoxin beta receptor blockers for COPD which reduce lung epithelial cell death and lung inflammation.
The automatic activation of Wnt signaling could then induce lung tissue regeneration.
In the first preclinical experiments, the group showed that the lymphotoxin beta receptor signaling in human lung tissue is identical to the signaling in mice.
This offers great potential for implementing lung regenerative medicine approaches in the clinic.
To achieve this ultimate goal, the researchers aim to test this novel therapeutic approach in human clinical trials over the coming years.
One author of the study is Dr. Ali Önder Yildirim.
The study is published in Nature.
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