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Updated: May 13, 2026
Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study
Published on: April 11, 2018
Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis
1CFTR Biomarker Centre and Translational CF Research Group Christiane Herzog Cystic Fibrosis Centre, Paediatric Pulmonology and Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany. Nico.Derichs@charite.de
Abstract:
Cystic fibrosis (CF) is caused by genetic mutations that affect the cystic fibrosis transmembrane conductance regulator (CFTR) protein. These mutations can impact the synthesis and transfer of the CFTR protein to the apical membrane of epithelial cells, as well as influencing the gating or conductance of chloride and bicarbonate ions through the channel. CFTR dysfunction results in ionic imbalance of epithelial secretions in several organ systems, such as the pancreas, gastrointestinal tract, liver and the respiratory system. Since discovery of the CFTR gene in 1989, research has focussed on targeting the underlying genetic defect to identify a disease-modifying treatment for CF. Investigated management strategies have included gene therapy and the development of small molecules that target CFTR mutations, known as CFTR modulators. CFTR modulators are typically identified by high-throughput screening assays, followed by preclinical validation using cell culture systems. Recently, one such modulator, the CFTR potentiator ivacaftor, was approved as an oral therapy for CF patients with the G551D-CFTR mutation. The clinical development of ivacaftor not only represents a breakthrough in CF care but also serves as a noteworthy example of personalised medicine.
Insights
Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR modulators, like ivacaftor, offer a personalized medicine approach by targeting specific CFTR mutations for disease modification.
Area of Science:
- Biochemistry
- Genetics
- Pharmacology
Background:
- Cystic fibrosis (CF) arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, impacting protein function and ion transport.
- CFTR protein dysfunction leads to ionic imbalances in epithelial secretions across multiple organ systems, including the lungs, pancreas, and gastrointestinal tract.
Purpose of the Study:
- To review the development of CFTR modulators as a disease-modifying treatment strategy for cystic fibrosis.
- To highlight ivacaftor as a successful example of a CFTR potentiator and personalized medicine in CF care.
Main Methods:
- High-throughput screening assays for identifying potential CFTR modulators.
- Preclinical validation using cell culture systems to assess modulator efficacy.
- Clinical trials to evaluate the safety and effectiveness of approved CFTR modulators.
Main Results:
- Ivacaftor, a CFTR potentiator, has been approved for CF patients with the G551D-CFTR mutation.
- This approval signifies a breakthrough in CF treatment, demonstrating the potential of targeted therapies.
Conclusions:
- CFTR modulators represent a significant advancement in treating cystic fibrosis by addressing the underlying genetic defect.
- The success of ivacaftor underscores the growing importance and effectiveness of personalized medicine in managing genetic diseases like CF.
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