DISEASE CHARACTERISATION OF PEOPLE WITH CYSTIC FIBROSIS AND A MINIMAL FUNCTION MUTATION: DATA FROM THE ITALIAN REGISTRY

2021 ◽  
Author(s):  
Donatello Salvatore ◽  
Vincenzo Carnovale ◽  
Fabio Majo ◽  
Rita Padoan ◽  
Serena Quattrucci ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Minimal Function ◽  
Mutation Data

Patients with cystic fibrosis having a residual function mutation: Data from the Italian registry

2018 ◽  
Vol 54 (2) ◽  
pp. 150-157 ◽  
Author(s):  
Donatello Salvatore ◽  
Rita Padoan ◽  
Roberto Buzzetti ◽  
Annalisa Amato ◽  
Barbara Giordani ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Residual Function ◽  
Mutation Data

scholarly journals Tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for minimal function CFTR mutations

2020 ◽  
Vol 19 (6) ◽  
pp. 962-968 ◽  
Author(s):  
Anne Munck ◽  
Eitan Kerem ◽  
Helmut Ellemunter ◽  
Daniel Campbell ◽  
Linda T. Wang ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Minimal Function ◽  
Cftr Mutations

WS12.3 Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor in cystic fibrosis severe patients with the F508del/minimal function genotype

2021 ◽  
Vol 20 ◽  
pp. S23-S24
Author(s):  
V. Carnovale ◽  
P. Iacotucci ◽  
V. Terlizzi ◽  
C. Colangelo ◽  
P. Medio ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Minimal Function

Disease burden in people with cystic fibrosis heterozygous for F508del and a minimal function mutation

2021 ◽  
Author(s):  
Gregory S. Sawicki ◽  
Kate Van Brunt ◽  
Jason Booth ◽  
Evan Bailey ◽  
Stefanie J. Millar ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Disease Burden ◽  
Minimal Function

Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease with the Phe508del/minimal function genotype

2021 ◽  
pp. 106646
Author(s):  
Vincenzo Carnovale ◽  
Paola Iacotucci ◽  
Vito Terlizzi ◽  
Carmela Colangelo ◽  
Pietro Medio ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Minimal Function

scholarly journals 197 Ivacaftor improves linear growth in children with cystic fibrosis (CF) and a G551D-CTFR mutation: data from the ENVISION study

2016 ◽  
Vol 15 ◽  
pp. S101 ◽  
Author(s):  
M.S. Stalvey ◽  
M. Niknian ◽  
M. Higgins ◽  
V. Tarn ◽  
S.L. Heltshe ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Linear Growth ◽  
Mutation Data

scholarly journals Nanomolar-potency ‘co-potentiator’ therapy for cystic fibrosis caused by a defined subset of minimal function CFTR mutants

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Puay-Wah Phuan ◽  
Joseph-Anthony Tan ◽  
Amber A. Rivera ◽  
Lorna Zlock ◽  
Dennis W. Nielson ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Class Ii ◽  
Bronchial Epithelial Cell ◽  
Therapeutic Benefit ◽  
Initial Structure ◽  
Transmembrane Conductance Regulator ◽  
Loss Of Function ◽  
Nonsense Mutations ◽  
Minimal Function ◽  
Cftr Mutations

AbstractAvailable CFTR modulators provide no therapeutic benefit for cystic fibrosis (CF) caused by many loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, including N1303K. We previously introduced the concept of ‘co-potentiators’ (combination-potentiators) to rescue CFTR function in some minimal function CFTR mutants. Herein, a screen of ~120,000 drug-like synthetic small molecules identified active co-potentiators of pyrazoloquinoline, piperidine-pyridoindole, tetrahydroquinoline and phenylazepine classes, with EC50 down to ~300 nM following initial structure-activity studies. Increased CFTR chloride conductance by up to 8-fold was observed when a co-potentiator (termed ‘Class II potentiator’) was used with a classical potentiator (‘Class I potentiator’) such as VX-770 or GLPG1837. To investigate the range of CFTR mutations benefitted by co-potentiators, 14 CF-associated CFTR mutations were studied in transfected cell models. Co-potentiator efficacy was found for CFTR missense, deletion and nonsense mutations in nucleotide binding domain-2 (NBD2), including W1282X, N1303K, c.3700A > G and Q1313X (with corrector for some mutations). In contrast, CFTR mutations G85E, R334W, R347P, V520F, R560T, A561E, M1101K and R1162X showed no co-potentiator activity, even with corrector. Co-potentiator efficacy was confirmed in primary human bronchial epithelial cell cultures generated from a N1303K homozygous CF subject. The Class II potentiators identified here may have clinical benefit for CF caused by mutations in the NBD2 domain of CFTR.

scholarly journals Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 828
Author(s):  
Marika Comegna ◽  
Vito Terlizzi ◽  
Donatello Salvatore ◽  
Carmela Colangelo ◽  
Antonella Miriam Di Lullo ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Personalized Medicine ◽  
Epithelial Cells ◽  
The Other ◽  
Nasal Epithelial Cells ◽  
Minimal Function ◽  
Functional Studies ◽  
Rare Mutations ◽  
Clinical Benefits ◽  
And Personalized Medicine

The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 6 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the other allele. However, there is a group of patients, in addition to those with rare mutations, in which despite the presence of a F508del in one allele, it was not possible to identify any mutation in the other allele. To date, these patients are excluded from treatment with Trikafta in Italy, where the CF patients carrying F508del/unknown represent about 1.3% (71 patients) of the overall Italian CF patients. In this paper we show that the Trikafta treatment of nasal epithelial cells, derived from F508del/Unknown patients, results in a significant rescue of CFTR activity. Based on our findings, we think that the F508del/Unknown patients considered in this study could obtain clinical benefits from Trikafta treatment, and we strongly suggest their eligibility for this type of treatment. This study, adding further evidence in the literature, once again confirms the validity of functional studies on nasal cells in the cystic fibrosis theratyping and personalized medicine.

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