Treatment of Cystic Fibrosis Patients Homozygous for <i>F508del</i> with Lumacaftor-Ivacaftor (Orkambi<sup>®</sup>) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells

Treatment of Cystic Fibrosis Patients Homozygous for <i>F508del</i> with Lumacaftor-Ivacaftor (Orkambi<sup>®</sup>) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells

The treatment of cystic fibrosis (CF) patients homozygous for the <i>F508del</i> mutation with Orkambi<sup>®</sup>, a combination of a corrector (lumacaftor) and a potentiator (ivacaftor) of the mutated CFTR protein, resulted in some amelioration of the respiratory function....

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Bibliographic Details
Main Authors: Maria Favia, Crescenzio Gallo, Lorenzo Guerra, Domenica De Venuto, Anna Diana, Angela Maria Polizzi, Pasqualina Montemurro, Maria Addolorata Mariggiò, Giuseppina Leonetti, Antonio Manca, Valeria Casavola, Massimo Conese
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:International Journal of Molecular Sciences
Subjects:
cystic fibrosis
Orkambi<sup>®</sup>
CFTR
mononuclear cells
BMI
sweat chloride
Online Access:https://www.mdpi.com/1422-0067/21/7/2398
Description
Summary:The treatment of cystic fibrosis (CF) patients homozygous for the <i>F508del</i> mutation with Orkambi<sup>®</sup>, a combination of a corrector (lumacaftor) and a potentiator (ivacaftor) of the mutated CFTR protein, resulted in some amelioration of the respiratory function. However, a great variability in the clinical response was also observed. The aim of this study was to evaluate the response to Orkambi<sup>®</sup> in a small cohort of F508del/F508del patients (<i>n</i> = 14) in terms of clinical and laboratory parameters, including ex vivo CFTR activity in mononuclear cells (MNCs), during a 12-month treatment. Patients responded with an increase in percent predicted forced expiratory volume in 1 s (FEV<sub>1</sub>%) and body mass index (BMI) as well as with a decrease in white blood cell (WBC) total counts and serum C-reactive protein (CRP) levels, although not significantly. Sweat chloride and CFTR-dependent chloride efflux were found to decrease and increase, respectively, as compared with pre-therapy values. CFTR and BMI showed a statistically significant correlation during Orkambi<sup>®</sup> treatment. Clustering analysis showed that CFTR, BMI, sweat chloride, FEV<sub>1</sub>%, and WBC were strongly associated. These data support the notion that CFTR-dependent chloride efflux in MNCs should be investigated as a sensitive outcome measure of Orkambi<sup>®</sup> treatment in CF patients.
ISSN:1661-6596
1422-0067

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