Changes of CFTR functional measurements and clinical improvements in cystic fibrosis patients with non p.Gly551Asp gating mutations treated with ivacaftor

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• 作者：Myriam Mesbahi^a ; ¹ ; Michal Shteinberg^b ; ^c ; ¹ ; Michael Wilschanski^d ; Aurelie Hatton^a ; Thao Nguyen&ndash ; Khoa^a ; Hannah Friedman^d ; Michael Cohen^d ; Virginie Escabasse^e ; Muriel Le Bourgeois^a ; Vicenzina Lucidi^f ; Isabelle Sermet-Gaudelus^f ; ^{Isabelle.sermet@aphp.fr} ; Laurence Bassinet^g ; ² ; Galit Livnat^b ; ^c ; ²
• 关键词：Cystic fibrosis ; Nasal potential difference ; Evaporimetry ; Short circuit current ; Ivacaftor ; CFTR modulators
• 刊名：Journal of Cystic Fibrosis
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：16
• 期：1
• 页码：45-48
• 全文大小：177 K
• 卷排序：16

文摘

Ivacaftor, a CFTR potentiator, has been found to improve CFTR function and clinical outcomes in patients with cystic fibrosis (CF) gating mutations. We investigated the effects of ivacaftor on CFTR functional measurement in CF patients carrying gating mutations other than p.Gly551Asp.Two siblings aged 13 and 12 carrying the p.Ser549Asn mutation, two sisters (45 and 43 years old) compound heterozygotes for p.Asp1152His and p.Gly1244Glu, a 37 year old man homozygous for the p.Gly1244Glu mutation, and a 7 year old girl with p.Arg352Gln and p.Gly1244Glu mutations commenced treatment with ivacaftor. NPD was performed in all the patients and approached normal for four patients who had also clinical improvement (p.Ser549Asn compound heterozygotes, and p.Asp1152His/p.Gly1244Glu siblings). Beta-adrenergic sweat chloride secretion performed in thep.Asp1152His/p.Gly1244Glu patients improved significantly. The p.Gly1244Glu mutation homozygous patient, who had undergone an ileal resection with ileostomy and enterocutaneous fistula, did not respond clinically to ivacaftor and did not modify his sweat test.These results highlight the importance of different CFTR activity measurements to explore CFTR modulator efficacy.