Surrogate Markers of Response to New Therapies in Cystic Fibrosis Patients

Personalized Therapy of Cystic Fibrosis: Set-up of Response Markers

The purpose of this study is to determine which biological marker, or association of biological markers, best predict clinical response of cystic fibrosis patients to CFTR modulators.

This study is based upon the hypothesis that clinical response of cystic fibrosis patients to CFTR modulators is correlated to in vitro responses to these drugs of epithelial cells derived from the patients, as assessed by CFTR-dependent Chloride secretion. Epithelial cells will be derived either from nasal or rectal epithelia, and consist both of cultured cells and organoids. The drugs tested will be Ivacaftor, or Lumacaftor/Ivacaftor, according to patient's treatment. Results of these assays will be compared with response to treatment at 6 and 12 months, assessed by clinical response and in vivo assay of CFTR function.

Inclusion Criteria:

• Cystic fibrosis patients treated by CFTR modulators (Ivacaftor or the association Ivacaftor-Lumacaftor)
• Cystic fibrosis patients non treated by CFTR modulators
• Patients in whom cystic fibrosis diagnosis has been suspected, but excluded by physiological and genetic investigations

Exclusion Criteria:

• pregnant or lactating women
• contraindication to nasal swab
• contraindication to rectal biopsy