Cystic Fibrosis Drug Effective for Some Patients

Reduces electrophysiological abnormalities

THURSDAY, Aug. 21 (HealthDay News) -- An oral drug that corrects the underlying genetic defect in some patients with cystic fibrosis can reduce the associated electrophysiological abnormalities, according to research published online Aug. 21 in The Lancet.

Eitan Kerem, M.D., from Hadassah Hebrew University Hospital in Jerusalem, Israel, and colleagues treated 23 adult patients with cystic fibrosis and at least one nonsense mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene with oral PTC124. In the first cycle, patients received a total of 16 mg/kg PTC124 per day for 14 days followed by 14 days without treatment; in the second cycle, patients received a total of 40 mg/kg PTC124 per day for 14 days followed by 14 days without treatment.

The researchers found that mean chloride transport, as assessed by transepithelial nasal potential difference, significantly increased in both treatment cycles. A response in total chloride transport, defined by a change in nasal potential difference of -5 mV or more, was observed in 16 (of 23) patients in the first cycle and in eight (of 21) patients in the second cycle. Total chloride transport was normalized in 13 (of 23) patients in the first cycle and in nine (of 21) patients in the second cycle. The drug was well tolerated, with adverse events including constipation without intestinal obstruction and mild dysuria, the report indicates. Treatment compliance was excellent.

"In patients with cystic fibrosis who have a premature stop codon in the CFTR gene, oral administration of PTC124 to suppress nonsense mutations reduces the epithelial electrophysiological abnormalities caused by CFTR dysfunction," Kerem and colleagues conclude.

The study was supported by PTC Therapeutics and Cystic Fibrosis Foundation Therapeutics.

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