This project is a good example of how basic research can serve as the basis for finding a promising therapeutic target to prevent the progression of a disease, in this case BOS, Bronchiolitis obliterans syndrome.
BOS is the main cause of chronic lung allograft dysfunction (CLAD) after lung transplantation. In this rejection reaction, the lung tissue hardens and scars and the function of the transplanted organ deteriorates. BOS reduces long-term survival and affects half of patients within five years.
The problem: Until now, it has been difficult to identify which patients will develop BOS. There are no recognisable symptoms or specific biomarkers/indications.
Scientists from Ali Önder Yildirim's group at the DZL site Munich have now found out that both in lung fluid from bronchoalveolar lavage and in the lung tissue of BOS patients, the activity of a certain enzyme, cathepsin B, is significantly increased. Furthermore, there is a correlation between cathepsin B activity and increased collagen formation, which in turn has a negative effect on lung function in BOS.
The researchers' hypothesis: Cathepsin B could be a promising therapeutic target to prevent the progression of BOS. This hypothesis will now be tested in a clinical trial that has already been approved by the German Centre for Lung Research (DZL).
Patients with lung transplants are to be studied in two steps until 20
- Retrospective study of patients who received a lung transplant between 2013 and 2015.
- Validating study of current lung transplant patients from January 2021 until the end of 2022 plus follow-up studies.
The aim is to use cathepsin B activity to develop a model to identify lung transplant recipients at risk of BOS within the first year after surgery. The early prediction of BOS could, in the next step, decisively improve the long-term survival of patients.
The study is also a model for the close and interdisciplinary collaboration of basic scientists and clinical researchers from different DZL sites, namely Munich (CPC-M, Dr. Ali Önder Yildirim) and Gießen (UGMLC, Prof. Matthias Hecker) and LMU clinic Munich (Dr. Nikolaus Kneidinger).