Precision medicine in cystic fibrosis: predictive role of forskolin-induced swelling assay

Extract People with cystic fibrosis (CF) carrying at least one copy of the F508del allele can benefit from a small molecule therapy referred to as cystic fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRm). The triple CFTRm combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to markedly improve clinical outcomes such as the percentage of predicted forced expiratory volume in 1 s (ppFEV1) and body mass index (BMI) [1]; however, granular data from the same clinical trial also showed that the treatment response to CFTRm varied among people with CF, even among those carrying the same CFTR genotype. To date, only short-circuit current measurements on human nasal epithelial cells have been validated as a predictive biomarker of CFTRm treatment response [2]. The forskolin-induced swelling assay (FIS) performed on patient-derived intestinal organoids (IOs) has been tested as another candidate tool for predicting the CFTRm response [3–5]. To date, no studies have compared the extent of FIS (i.e. numeric values of the area under the curve (AUC)) and the magnitude of clinical response to ELX/TEZ/IVA in real life. Thus, we investigated this correlation to assess whether the FIS can predict clinical outcomes in F508del homozygous people with CF treated with ELX/TEZ/IVA.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Research Letters Source Type: research