COPD is reversible
Chronic obstructive pulmonary disease (COPD) is one of the most common and severe diseases worldwide. More than 250 million people suffer from COPD. Ninety percent of patients with this disease are or have been chronic smokers. The components of tobacco smoke lead to fibrosis and death of lung epithelial cells – these are two key signs of COPD that prevent effective breathing. Modern methods of treatment are aimed at relieving shortness of breath, reducing cough and slowing the progression of COPD and related diseases. In severe cases, patients need lung transplantation.
Researchers from Helmholtz Zentrum München and the German Cancer Research Center (DKFZ) have successfully tested a new COPD treatment method on mice exposed to chronic cigarette smoke.
All attention is on tissue regeneration
One of the problems in developing COPD treatment methods is that the lungs cannot regenerate on their own. The research team focused on finding ways to trigger the regeneration of lung tissue and block the death of lung epithelial cells.
In 2009, researchers from DKFZ stopped chronic inflammation and fibrosis of liver tissue. To do this, they blocked the signaling pathway of the lymphotoxin-beta enzyme receptor in the liver, which is responsible for the activation and organization of immune cells, as well as for chronic liver inflammation leading to fibrosis. The authors suggested that blocking lymphotoxin-beta may also contribute to regenerative processes in other organs.
The pathogenesis of liver and lung diseases has a lot in common. In COPD, immune cells form so–called tertiary follicles - lymphoid infiltrates, which play an important role in the progression of the disease. To form these infiltrates, the lymphotoxin-beta receptor in the lungs must be activated – the same receptor that was affected in a 2009 study to restore the liver. The researchers blocked the lymphotoxin-beta signaling pathway in the lungs of mice that developed cigarette smoke-induced COPD with its typical lymphoid infiltrates, fibrosis and death of lung epithelial cells.
Complete restoration of lung tissue in mice
Blocking the signaling pathway of the lymphotoxin-beta receptor in the lung tissue of mice disrupted the formation of lymphoid infiltrates, prevented the death of lung epithelial cells and at the same time triggered the regeneration of lung tissue, which occurred despite the continued exposure to cigarette smoke. The researchers observed a complete recovery of lung tissue. Moreover, when the lungs of the mice recovered, COPD-related diseases, such as muscle wasting, also decreased.
The researchers found that regeneration of damaged lung epithelial cells is induced by activation of the Wnt signaling pathway, which is automatically triggered when the transmission of signals of the lymphotoxin-beta receptor in these cells is blocked. The Wnt signaling pathway is disabled in COPD, so the lung tissue is not restored. In previous experiments, it was proved that re-activation of Wnt in mice causes lung regeneration.
A new therapeutic approach
The idea of the researchers is to create a drug based on lymphotoxin-beta blockers for the treatment of COPD, which will reduce the death of epithelial cells and inflammation in the lungs. Automatic activation of the signaling Wnt will then trigger the regeneration of lung tissue.
In the first preclinical experiments, the group demonstrated that the transmission of signals of the lymphotoxin-beta receptor in human lung tissue is identical to the transmission of signals in mice. This gives reason to hope for the introduction of regenerative lung therapy into clinical practice.
Article by T.M.Conlon et al. Inhibition of LTßR signaling activates WNT-induced regeneration in lung is published in the journal Nature.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Helmholtz Zentrum München: Promising Therapeutic Approach against COPD.