title: A pilot study of the effect of gentamicin on nasal potential difference measurements in cystic fibrosis patients carrying stop mutations.
abstract: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene containing a premature termination signal are expected to produce little or no CFTR chloride channels. It has been shown in vitro, that aminoglycoside antibiotics can increase the frequency of erroneous insertion of nonsense codons hence permitting the translation of CFTR alleles carrying missense mutations to continue reading to the end of the gene. This led to the appearance of functional CFTR channels at the apical plasma membrane. The aim of this research was to determine if topical application of gentamicin to the nasal epithelium of patients with cystic fibrosis (CF) carrying stop mutations can express, in vivo, functional CFTR channels. Nine CF patients carrying stop mutations (mean age 23 +/- 11 yr, range 12 to 46 yr) received gentamicin drops (0.3%, 3 mg/ml) three times daily intranasally for a total of 14 d. Nasal potential difference (PD) was measured before and after the treatment. Before gentamicin application all the patients had abnormal nasal PD typical of CF. After gentamicin treatment, significant repolarization of the nasal epithelium representing chloride transport was increased from -1 +/- 1 mV to -10 +/- 11 mV (p < 0. 001). In conclusion, gentamicin may influence the underlying chloride transport abnormality in patients with CF carrying stop mutations.
authors.affiliation: Department of Pediatrics, Cystic Fibrosis Center, Shaare Zedek Medical Center, Hebrew University, Jerusalem, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Wilschanski
authors.forename: C
authors.initials: C
authors.lastname: Famini
authors.forename: H
authors.initials: H
authors.lastname: Blau
authors.forename: J
authors.initials: J
authors.lastname: Rivlin
authors.forename: A
authors.initials: A
authors.lastname: Augarten
authors.forename: A
authors.initials: A
authors.lastname: Avital
authors.forename: B
authors.initials: B
authors.lastname: Kerem
authors.forename: E
authors.initials: E
authors.lastname: Kerem
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D018118:Chloride Channels / Q000187:drug effects; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D020125:Mutation, Missense; D009297:Nasal Mucosa / Q000187:drug effects
chemical_list: C505032:CFTR protein, human; D018118:Chloride Channels; D005839:Gentamicins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator