Researchers from Charité, the Max Delbrück Center (MDC), and the Berlin Institute of Health (BIH) have investigated how modern CFTR modulators in cystic fibrosis affect not only the lungs but also the body’s overall proteome. The study, published in Cell Systems, provides new insights into the systemic effects of highly effective therapies.
CFTR modulators improve the function of the CFTR protein, which is commonly mutated in cystic fibrosis, and have fundamentally changed the treatment of the disease in recent years. In the current study, the researchers compared dual therapy (Lumacaftor/Ivacaftor) with the now established triple therapy (Elexacaftor/Tezacaftor/Ivacaftor).
The results show that the triple therapy in particular induces pronounced changes in the blood proteome and shifts it toward a healthier state, especially with regard to inflammatory and metabolic processes.
By combining analyses of blood and sputum samples, the researchers were also able to demonstrate that local changes in the lungs and systemic effects throughout the body only partially overlap. These findings provide important new insights into molecular disease mechanisms and the development of novel biomarkers.
Particularly noteworthy is the protein SFTPB (Surfactant Protein B), which closely correlates with lung function and shows reproducible changes under therapy. The findings were additionally confirmed in an independent cohort.
The study was led by Dr. Kerstin Fentker and conducted in collaboration with senior authors and DZL scientists Dr. Simon Gräber and Prof. Marcus Mall, as well as Dr. Philipp Mertins.
Original publication: Fentker K, Kirchner M, Ziehm M, Niquet S, Popp O, Duerr J, Schaupp L, Roehmel J, Thee S, Hämmerling S, Sommerburg O, Stahl M, Graeber SY, Mall MA, Mertins P. Systemic effects of cystic fibrosis transmembrane conductance regulator modulators on the plasma and serum proteome. Cell Syst. 2026 May 20;17(5):101569. doi: 10.1016/j.cels.2026.101569. Epub 2026 Apr 1. PMID: 41928517.
