PMID- 21349786
OWN - NLM
STAT- MEDLINE
DCOM- 20110915
LR  - 20121115
IS  - 2210-741X (Electronic)
IS  - 2210-7401 (Linking)
VI  - 35
IP  - 4
DP  - 2011 Apr
TI  - Molecular repair of a defective CFTR protein in cystic fibrosis.
PG  - 254-6
LID - 10.1016/j.clinre.2011.01.003 [doi]
AB  - We analyse a paper, which reports an entirely novel approach to the treatment of 
      cystic fibrosis, consisting in "repairing" the defective mutant protein. Patients 
      with cystic fibrosis have a mutation of the gene encoding the cystic fibrosis 
      transmembrane conductance regulator (CFTR), an epithelial chloride channel 
      involved in salt and fluid transport in multiple organs, including the lungs and 
      pancreas. The mutations have different effects on the CFTR protein, such as 
      misfolding for the DeltaF508 mutation (the most common), or defective opening of the 
      chloride channel for the G551D-CFTR mutation, found in 4 to 5% of the patients. 
      The authors of this work have shown that VX-770, an agent known previously to 
      increase the activity of wild-type and G551D-CFTR cell surface protein in vitro, 
      was able, when given orally to 39 cystic fibrosis patients during 14 and 28 days, 
      to partially restore chloride conductance, as measured by nasal epithelium 
      potential difference. Similarly, the agent partially restored chloride transport 
      in sweat glands, as measured by the sweat chloride concentration. Clinically, 
      VX-770 increased the forced expiratory volume per second (FEVi). Side effects 
      included macular skin rash, elevation of blood glucose concentration and 
      glycosuria. All side effects resolved after discontinuation of the drug. VX-770 
      has also been shown to increase the activity of DeltaF508-CFTR channels in vitro, 
      provided they reach the cell surface. This study appears to be a milestone in the 
      treatment of cystic fibrosis and possibly other genetic diseases.
CI  - Copyright (c) 2011 Elsevier Masson SAS. All rights reserved.
FAU - Erlinger, S
AU  - Erlinger S
AD  - University of Paris 7, Paris, France. serge.erlinger@gmail.com
LA  - eng
PT  - Journal Article
DEP - 20110223
PL  - France
TA  - Clin Res Hepatol Gastroenterol
JT  - Clinics and research in hepatology and gastroenterology
JID - 101553659
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
SB  - IM
MH  - Cystic Fibrosis/*genetics/*therapy
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/*genetics
MH  - Forecasting
MH  - *Genetic Therapy
MH  - Humans
MH  - Mutation
EDAT- 2011/02/26 06:00
MHDA- 2011/09/16 06:00
CRDT- 2011/02/26 06:00
PHST- 2010/12/02 00:00 [received]
PHST- 2011/01/17 00:00 [accepted]
PHST- 2011/02/26 06:00 [entrez]
PHST- 2011/02/26 06:00 [pubmed]
PHST- 2011/09/16 06:00 [medline]
AID - S2210-7401(11)00019-2 [pii]
AID - 10.1016/j.clinre.2011.01.003 [doi]
PST - ppublish
SO  - Clin Res Hepatol Gastroenterol. 2011 Apr;35(4):254-6. doi: 
      10.1016/j.clinre.2011.01.003. Epub 2011 Feb 23.