Primary Nasal Cell Culture as a Tool for Personalized Therapy in Cystic Fibrosis

Study Overview
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Brief Summary
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characterization of CFTR function and expression in nasal primary cells collected from patients with cystic fibrosis in comparison to their parents, healthy heterozygotes and healthy controls

Detailed Description
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3 groups of subjects are enrolled CF subjects according to their genotypes (aiming to enroll patients carrying 2 CF causing mutations with no CFTR expression/function, and patients carrying at least 1 mutation with residual function, such R117H) Parents or siblings of the CF subjects, as healthy hétérozygotes healthy controls All these subjects experience nasal brushings. From these nasal brushings,nasal cells are expanded, and cultured in air liquid interface to obtain polarized epithelium. This epithelium is then studied in Ussing chamber experiments to characterize the level of cAMP dependant Chloride transport and Sodium reabsorption. Apical expression of CFTR is assessed by immunofluorescence. Results will allow to define the variability of CFTR function and expression criteria in subjects with the same genotype. Such data are crucial for interpretation of the effect of CFTR modulators.

Official Title
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Evaluation of the Primary Human Nasal Epithelial Cell Culture Model in the Context of Personalized Therapy in Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Procedure: cell sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with Cystic Fibrosis with 2 mutations in CFTR healthy heterozygotes with 1 mutation in CFTR healthy subjects with no familial history of Cystic Fibrosis and no symptoms suggesting Cystic Fibrosis Exclusion Criteria: smoking
Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| cystic fibrosis patients<br>Cystic fibrosis patients carrying to 2 CFTR mutations undergoing cell sampling | Procedure: cell sampling<br>* nasal brushing to collect cells<br>|
| healthy heterozygotes<br>healthy heterozygotes carrying 1 CFTR mutations undergoing cell sampling | Procedure: cell sampling<br>* nasal brushing to collect cells<br>|
| healthy control<br>subject with no evidence of any symptoms compatible with Cystic Fibrosis undergoing cell sampling | Procedure: cell sampling<br>* nasal brushing to collect cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| variation in the short-circuit-current (Isc) after Forskolin (Forskolin)/IBMx and VX-770 (∆IscFsk/IBMx+VX-770) | The short-circuit-current (Isc) was measured under voltage clamp conditions. Inhibitors and activators were added after stabilization of baseline Isc. The sum of the change after Forskolin (Forskolin)/IBMx and VX-770 (∆IscFsk/IBMx+VX-770) served as an index of CFTR function. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of cells displaying apical staining | CFTR immuno-detection was performed as previously described 31. Apical CFTR staining was assessed semi quantitatively as the percentage of cells displaying apical staining multiplied by the average corrected apical fluorescence 32. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biomarker