A pilot study of the effect of gentamicin on nasal potential difference measurements in cystic fibrosis patients carrying stop mutations

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene containing a premature termination signal are expected to produce lit tle or no CFTR chloride channels. It has been shown in vitro, that aminogly coside antibiotics can increase the frequency of erroneous insertion of non sense codons hence permitting the translation of CFTR alleles carrying miss ense 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 a im of this research was to determine if topical application of gentamicin t o 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 tota l of 14 d. Nasal potential difference (PD) was measured before and after th e treatment. Before gentamicin application all the patients had abnormal na sal PD typical of CF. After gentamicin treat ment, significant repolarizati on of the nasal epithelium representing chloride transport was increased fr om -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.