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

Autor: Lorenzo Guerra, Anna Diana, Giuseppina Leonetti, Angela Polizzi, Massimo Conese, Maria Addolorata Mariggiò, Valeria Casavola, Maria Favia, Antonio Manca, Domenica De Venuto, Pasqualina Montemurro, Crescenzio Gallo
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
medicine.medical_specialty
congenital
hereditary
and neonatal diseases and abnormalities
chemical and pharmacologic phenomena
FEV1%
Peripheral blood mononuclear cell
Cystic fibrosis
Catalysis
Inorganic Chemistry
Ivacaftor
cystic fibrosis
lcsh:Chemistry
03 medical and health sciences
chemistry.chemical_compound
BMI
0302 clinical medicine
immune system diseases
White blood cell
Internal medicine
hemic and lymphatic diseases
medicine
Respiratory function
Physical and Theoretical Chemistry
CFTR
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
mononuclear cells
Orkambi®
business.industry
Organic Chemistry
Lumacaftor
hemic and immune systems
General Medicine
Potentiator
medicine.disease
Computer Science Applications
030104 developmental biology
medicine.anatomical_structure
Endocrinology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
030220 oncology & carcinogenesis
business
sweat chloride
Ex vivo
medicine.drug
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 2398, p 2398 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 7
ISSN: 1661-6596
1422-0067
Popis: 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 (FEV1%) 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, FEV1%, 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.
Databáze: OpenAIRE
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