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

The treatment of cystic fibrosis (CF) patients homozygous for the F508del mutation with Orkambi(®), 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 clin...

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Detalles Bibliográficos
Autores principales: Favia, Maria, Gallo, Crescenzio, Guerra, Lorenzo, De Venuto, Domenica, Diana, Anna, Polizzi, Angela Maria, Montemurro, Pasqualina, Mariggiò, Maria Addolorata, Leonetti, Giuseppina, Manca, Antonio, Casavola, Valeria, Conese, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177453/
https://www.ncbi.nlm.nih.gov/pubmed/32244302
http://dx.doi.org/10.3390/ijms21072398
Descripción
Sumario:The treatment of cystic fibrosis (CF) patients homozygous for the F508del mutation with Orkambi(®), 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(®) in a small cohort of F508del/F508del patients (n = 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(1)%) 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(®) treatment. Clustering analysis showed that CFTR, BMI, sweat chloride, FEV(1)%, 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(®) treatment in CF patients.