ABCMdb

PMID: 21233271

Wilschanski M, Miller LL, Shoseyov D, Blau H, Rivlin J, Aviram M, Cohen M, Armoni S, Yaakov Y, Pugatch T, Cohen-Cymberknoh M, Miller NL, Reha A, Northcutt VJ, Hirawat S, Donnelly K, Elfring GL, Ajayi T, Kerem E
Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis.
Eur Respir J. 2011 Jul;38(1):59-69. Epub 2011 Jan 13., [PubMed]

Sentences

No. Mutations Sentence Comment

91 ABCC7 p.Trp1282* Three nonsense mutation genotypes were represented, with W1282X being the most common. Login to comment 104 ABCC7 p.Trp1282* ABCC7 p.Gly542* Ataluren treatment was associated with an on-treatment total chloride response in both patients with the G542X and W1282X mutations. Login to comment 110 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* Changes in total chloride transport were TABLE 1 Baseline patient characteristics Ataluren dose level Low# High" Combined Age yrs 21 (19-57) 27 (19-45) 26 (19-57) Sex Male 8 2 10 Female 4 5 9 BMI 22.3 (15.4-27.8) 21.8 (19.0-26.6) 21.8 (15.4-27.8) Sweat chloride+ mEq?L-1 88 (47-109) 89 (49-106) 88 (47-109) Nasal total chloride transport1 mV 1.6 (-1.6-9.3) -0.3 (-2.3-1.9) 0.7 (-2.3-9.3) Pulmonary function % prede FEV1 64 (44-106) 65 (46-92) 65 (44-106) FVC 82 (63-109) 77 (57-101) 78 (57-109) Pathological lung infection 12 6 18 Pseudomonas aeruginosa 11 6 17 Mycobacterium abscessus 2 0 2 Methicillin-resistant Staphylococcus aureus 1 0 1 None 0 1 1 Pancreatic insufficiency Exocrine 11 6 17 Endocrine 2 5 7 Abnormalities of liver-related serum parameters 3 2 5 ALT 0 2 2 AST 1 0 1 Alkaline phosphatase 2 1 3 GGT 0 0 0 Bilirubin 1 0 1 LDH 1 0 1 Genotype allele 1/allele 2 G542X (UGA)/DF508 2 0 2 G542X (UGA)/W1282X (UGA) 0 1 1 G542X (UGA)/N1303K 0 1 1 W1282X (UGA)/DF508 8 2 10 W1282X (UGA)/W1282X (UGA) 1 2 3 W1282X (UGA)/3849+10kB CRT## (UAA) 0 1 1 3849+10kB CRT## (UAA)/DF508 1 0 1 Time from last ataluren dose in prior study months 10.5 (9.3-12.2) 10.5 (8.5-11.5) 10.5 (8.5-12.2) Data are presented as n or median (range). Login to comment 121 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* Rather than using the mean NPD values obtained from both nostrils (as in the primary analyses), we also analysed outcome 5 0 Response -5 -15 -10 Changefrombaseline totalchloridetransportmV CFTR mutation type G542X/ΔF508 W1282X/ΔF508 W1282X/ΔF508 W1282X/ΔF508 W1282X/ΔF508 W1282X/ΔF508 W1282X/ΔF508 W1282X/ΔF508 W1282X/ΔF508 W1282X/ΔF508 W1282X/G542X W1282X/W1282X W1282X/W1282X W1282X/W1282X G542X/N1303K G542X/ΔF508 W1282X/ΔF508 W1282X/3849+10KBC→T 4, 4 and 8 mg·kg-1 (n=11) 10, 10 and 20 mg·kg-1 (n=7) FIGURE 1. Login to comment 191 ABCC7 p.Trp1282* ABCC7 p.Gly542* Total chloride transport improvements were noted in patients with both G542X and W1282X premature stop codon mutations, confirming data from our prior study [20] and from other ataluren trials [42], indicating that multiple nonsense mutation genotypes can be responsive to ataluren therapy. Login to comment