A study led by researchers from the German Center for Lung Research (DZL) at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin shows that triple therapy can almost completely restore the function of defective CFTR channels in children with cystic fibrosis. The effect was particularly pronounced in younger children. The findings highlight the potential benefits of starting treatment as early as possible. Researchers from the DZL site TLRC in Heidelberg also contributed to the study.<\/p>\n
Cystic fibrosis (CF) is an incurable inherited disease in which certain molecular structures in the body\u2019s epithelial tissues, known as CFTR channels, do not function properly or function only to a limited extent due to a genetic defect. This can lead to thick mucus in the lungs, recurrent respiratory infections, and complications affecting other organs.<\/p>\n
For several years, a causal treatment known as triple therapy has been available. It combines the active ingredients elexacaftor, tezacaftor and ivacaftor and is now also approved for children aged two years and older.<\/p>\n
The research team studied 26 children with cystic fibrosis between the ages of two and eleven. In addition to lung function, sweat tests and nutritional parameters, the researchers directly assessed CFTR channel function. To do so, they collected small samples of intestinal tissue and analysed chloride transport in the epithelial cells.<\/p>\n
The study included Dr Simon Gr\u00e4ber, DZL Principal Investigator at the Charit\u00e9 site and head of the junior research group \u201cPrecision Medicine in Cystic Fibrosis\u201d at the Department of Paediatric Respiratory Medicine, Immunology and Critical Care at Charit\u00e9.<\/p>\n
\u201cThe result was remarkable: triple therapy restored CFTR channel function to 90 to 100 percent,\u201d explains Simon Gr\u00e4ber. This means that the treated children reached values close to those seen in children without cystic fibrosis.<\/p>\n
The findings are particularly noteworthy when compared with previous studies in adolescents and adults. Restoration of CFTR function was significantly greater in younger children. \u201cWe found a clear age dependency: the younger the patient, the greater the effect,\u201d says Simon Gr\u00e4ber.<\/p>\n
The results provide important mechanistic evidence for why starting treatment as early as possible could be particularly promising in cystic fibrosis. If early treatment can prevent disease processes and irreversible changes, particularly in the lungs, it could help further improve long-term outcomes.<\/p>\n
The current findings complement earlier studies by the research team led by Prof Marcus Mall, which had already shown that children benefit substantially from triple therapy, with improvements in lung function and changes in lung tissue. The new study now provides a possible explanation at the level of CFTR function.<\/p>\n
In further studies, the researchers plan to use single-cell analyses to investigate how triple therapy works at the molecular level in epithelial cells. They also aim to determine whether starting treatment even earlier \u2013 for example, from the first year of life \u2013 could help prevent disease-related changes even more effectively.<\/p>\n