Press Release

03.02.2021

Bronchiolitis Obliterans - DZL approves clinical trial

From basic research to clinical study

Bronchiolitis obliterans syndrome (BOS) is the main manifestation of chronic lung allograft dysfunction (CLAD). It leads to poor long-term survival after lung transplantation, affecting 50% of patients within five years. In current diagnostic practice, the recognition of early allograft dysfunction is limited due to the absence of symptoms and specific measures or biomarkers.

Researchers Carmela Morrone and Aicha Jeridi from the Yildirim Lab at ILBD/CPC-M showed in a recent paper that there is a significant increase of Cathepsin B activity in bronchoalveolar lavage fluid and lung tissue from BOS patients. Moreover, Cathepsin B activity was associated with an increased biosynthesis of collagen, and negatively affected lung function, driving BOS development. Thus, Cathepsin B represents a promising therapeutic target to prevent the progression of BOS.

Clinicial trial: Cathepsin-B (CatB) as a new biomarker and therapeutic target for early bronchiolotis obliterans syndrome (BOS) after lung transplantation

 To validate the findings, the group set up a clinical study that is approved by the German Center of Lung Research (DZL). In this study, the main aim is to determine the catalytic activities and expression of CatB simultaneously with Cathepsin-L and -S as well as the cysteine proteinase inhibitor to develop a predictive model. This could make it possible to identify lung transplant recipients with a risk of developing BOS within the first year after surgery. The results are expected to extend into an interventional study where CatB activity and expression will be used to monitor graft function and ultimately be targeted in a prophylactic or therapeutic approach.

The project demonstrates a best practice example of how basic and translational research is translated into clinical study design. Moreover, it is made feasible by the close and interdisciplinary interaction of basic scientists and clinical researchers from different institutes/DZL sites, namely Munich (CPC-M) and Giessen (UGMLC).

Original publication:

https://pubmed.ncbi.nlm.nih.gov/33303550/