Lung Enzyme Cathepsin S is New Therapeutic Target for CF and COPD

Vijaya Iyer, PhD avatar

by Vijaya Iyer, PhD |

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Blocking the enzyme cathepsin S can alleviate symptoms and reduce lung damage in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), according to multinational teams led by researchers at Queen’s University Belfast, U.K.

The findings on CF were reported in the study “Targeting of Cathepsin S Reduces Cystic Fibrosis-like Lung Disease,” published in the European Respiratory Journal; the data on COPD was published in the American Journal of Respiratory and Critical Care Medicine, in an article titled “Protein Phosphatase 2A Reduces Cigarette Smoke-Induced Cathepsin S and Loss of Lung Function.

High levels of cathepsin S have been reported previously in the lungs of both CF and COPD patients, and they have been linked to increased inflammation and lung tissue scarring.

“We know that this enzyme plays a key role in provoking symptoms of chronic lung diseases such as CF and COPD,” Cliff Taggart, PhD, said in a press release. Taggart is lead scientist and professor at Wellcome-Wolfson Centre for Experimental Medicine at Queen’s University.

“We have now discovered that treatment to target this specific enzyme can significantly reduce inflammation, lung damage, and mucus obstruction, key hallmark features of CF and COPD,” Taggart added.

In the first study, researchers used a CF mouse model and tested a cathepsin S blocking agent, called VBY-999. Results showed that animals treated with VBY-999 had a significant reduction in lung inflammation and damage, as well as in mucus obstruction.

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In contrast, experimentally inducing high levels of cathepsin S in a healthy mouse triggered increased mucus production, inflammation, and damage to the lungs, the team noted.

Cathepsin S performs its activity with the help of a receptor protein called PAR-2. The team showed that in CF mice, blocking PAR-2 also alleviated lung disease symptoms, confirming a vital role for cathepsin S in lung damage.

In the COPD study, researchers showed that blocking cathepsin S using the protein phosphatase 2A enzyme alleviated lung symptoms associated with cigarette smoke-induced COPD.

Both studies confirmed that cathepsin S is a feasible therapeutic target for new treatments in these two lung diseases.

“There is a high unmet need for effective anti-inflammatory therapies for patients with these chronic lung diseases, and targeting of cathepsin S is a promising strategy that can now be tested in future clinical trials,” said Marcus Mall, professor at Charité Universitätsmedizin Berlin and co-author of the CF study.

“Thanks to this research, we now understand the causes and how to reduce the symptoms associated with both CF and COPD,” added Sinéad Weldon, PhD, a lead author of the two studies.

“Moving forward, we need to apply this knowledge in further testing so that ultimately, we can improve the quality of life for those affected by these diseases,” Weldon said.

Of note, Queen’s University Belfast researchers conducted the CF study in collaboration with researchers from Charité Universitätsmedizin Berlin, Virobay, and INSERM Paris; and the COPD study in collaboration with scientists at the State University of New York in Brooklyn, and Imperial College London, U.K.