***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In a subset of patients with cystic fibrosis ( CF ) , nonsense mutations ( premature stop codons ) disrupt production of full-length , functional CF transmembrane conductance regulator ( CFTR ) . Ataluren ( PTC124 ) allows ribosomal readthrough of premature stop codons in mRNA . We evaluated drug activity and safety in patients with nonsense mutation CF who took ataluren three times daily ( morning , midday and evening ) for 12 weeks at either a lower dose ( 4 , 4 and 8 mg·kg−1 ) or higher dose ( 10 , 10 and 20 mg·kg−1 ) . The study enrolled 19 patients ( 10 males and nine females aged 19–57 yrs ; dose : lower 12 , higher seven ) with a classic CF phenotype , at least one CFTR nonsense mutation allele , and an abnormal nasal total chloride transport .  Both ataluren doses were similarly active , improving total chloride transport with a combined mean change of -5.4 mV ( p<0.001 ) , and on-treatment responses ( at least -5 mV improvement ) and hyperpolarisations ( values more electrically negative than -5 mV ) in 61 % ( p<0.001 ) and 56 % ( p = 0.002 ) of patients . CFTR function was greater with time and was accompanied by trends toward improvements in pulmonary function and CF-related coughing . Adverse clinical and laboratory findings were uncommon and usually mild . Chronic ataluren administration produced time-dependent improvements in CFTR activity and clinical parameters with generally good tolerability BACKGROUND Ataluren was developed to restore functional protein production in genetic disorders caused by nonsense mutations , which are the cause of cystic fibrosis in 10 % of patients . This trial was design ed to assess the efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis . METHODS This r and omised , double-blind , placebo-controlled , phase 3 study enrolled patients from 36 sites in 11 countries in North America and Europe . Eligible patients with nonsense-mutation cystic fibrosis ( aged ≥ 6 years ; abnormal nasal potential difference ; sweat chloride > 40 mmol/L ; forced expiratory volume in 1 s [ FEV1 ] ≥ 40 % and ≤ 90 % ) were r and omly assigned by interactive response technology to receive oral ataluren ( 10 mg/kg in morning , 10 mg/kg midday , and 20 mg/kg in evening ) or matching placebo for 48 weeks . R and omisation used a block size of four , stratified by age , chronic inhaled antibiotic use , and percent-predicted FEV1 . The primary endpoint was relative change in percent-predicted FEV1 from baseline to week 48 , analysed in all patients with a post-baseline spirometry measurement . This study is registered with Clinical Trials.gov , number NCT00803205 . FINDINGS Between Sept 8 , 2009 , and Nov 30 , 2010 , 238 patients were r and omly assigned , of whom 116 in each treatment group had a valid post-baseline spirometry measurement . Relative change from baseline in percent-predicted FEV1 did not differ significantly between ataluren and placebo at week 48 ( -2.5 % vs -5.5 % ; difference 3.0 % [ 95 % CI -0.8 to 6.3 ] ; p=0.12 ) . The number of pulmonary exacerbations did not differ significantly between treatment groups ( rate ratio 0.77 [ 95 % CI 0.57 - 1.05 ] ; p=0.0992 ) . However , post-hoc analysis of the subgroup of patients not using chronic inhaled tobramycin showed a 5.7 % difference ( 95 % CI 1.5 - 10.1 ) in relative change from baseline in percent-predicted FEV1 between the ataluren and placebo groups at week 48 ( -0.7 % [ -4.0 to 2.1 ] vs -6.4 % [ -9.8 to -3.7 ] ; nominal p=0.0082 ) , and fewer pulmonary exacerbations in the ataluern group ( 1.42 events [ 0.9 - 1.9 ] vs 2.18 events [ 1.6 - 2.7 ] ; rate ratio 0.60 [ 0.42 - 0.86 ] ; nominal p=0.0061 ) . Safety profiles were generally similar for ataluren and placebo , except for the occurrence of increased creatinine concentrations ( ie , acute kidney injury ) , which occurred in 18 ( 15 % ) of 118 patients in the ataluren group compared with one ( < 1 % ) of 120 patients in the placebo group . No life-threatening adverse events or deaths were reported in either group . INTERPRETATION Although ataluren did not improve lung function in the overall population of nonsense-mutation cystic fibrosis patients who received this treatment , it might be beneficial for patients not taking chronic inhaled tobramycin . FUNDING PTC Therapeutics , Cystic Fibrosis Foundation , US Food and Drug Administration 's Office of Orphan Products Development , and the National Institutes of Health BACKGROUND In about 10 % of patients worldwide and more than 50 % of patients in Israel , cystic fibrosis results from nonsense mutations ( premature stop codons ) in the messenger RNA ( mRNA ) for the cystic fibrosis transmembrane conductance regulator ( CFTR ) . PTC124 is an orally bioavailable small molecule that is design ed to induce ribosomes to selectively read through premature stop codons during mRNA translation , to produce functional CFTR . METHODS This phase II prospect i ve trial recruited adults with cystic fibrosis who had at least one nonsense mutation in the CFTR gene . Patients were assessed in two 28-day cycles . During the first cycle , patients received PTC124 at 16 mg/kg per day in three doses every day for 14 days , followed by 14 days without treatment ; in the second cycle , patients received 40 mg/kg of PTC124 in three doses every day for 14 days , followed by 14 days without treatment . The primary outcome had three components : change in CFTR-mediated total chloride transport ; proportion of patients who responded to treatment ; and normalisation of chloride transport , as assessed by transepithelial nasal potential difference ( PD ) at baseline , at the end of each 14-day treatment course , and after 14 days without treatment . The trial was registered with who.int/ictrp , and with clinical trials.gov , number NCT00237380 . FINDINGS Transepithelial nasal PD was evaluated in 23 patients in the first cycle and in 21 patients in the second cycle . Mean total chloride transport increased in the first treatment phase , with a change of -7.1 ( SD 7.0 ) mV ( p<0.0001 ) , and in the second , with a change of -3.7 ( SD 7.3 ) mV ( p=0.032 ) . We recorded a response in total chloride transport ( defined as a change in nasal PD of -5 mV or more ) in 16 of the 23 patients in the first cycle 's treatment phase ( p<0.0001 ) and in eight of the 21 patients in the second cycle ( p<0.0001 ) . Total chloride transport entered the normal range for 13 of 23 patients in the first cycle 's treatment phase ( p=0.0003 ) and for nine of 21 in the second cycle ( p=0.02 ) . Two patients given PTC124 had constipation without intestinal obstruction , and four had mild dysuria . No drug-related serious adverse events were recorded . INTERPRETATION 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 BACKGROUND Mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene containing a premature termination signal cause a deficiency or absence of functional chloride-channel activity . Aminoglycoside antibiotics can suppress premature termination codons , thus permitting translation to continue to the normal end of the transcript . We assessed whether topical administration of gentamicin to the nasal epithelium of patients with cystic fibrosis could result in the expression of functional CFTR channels . METHODS In a double-blind , placebo-controlled , crossover trial , patients with stop mutations in CFTR or patients homozygous for the DeltaF508 mutation received two drops containing gentamicin ( 0.3 percent , or 3 mg per milliliter ) or placebo in each nostril three times daily for two consecutive periods of 14 days . Nasal potential difference was measured at base line and after each treatment period . Nasal epithelial cells were obtained before and after gentamicin treatment from patients carrying stop mutations , and the C-terminal of surface CFTR was stained . RESULTS Gentamicin treatment caused a significant reduction in basal potential difference in the 19 patients carrying stop mutations ( from -45+/-8 to -34+/-11 mV , P=0.005 ) and a significant response to chloride-free isoproterenol solution ( from 0+/-3.6 to -5+/-2.7 mV , P<0.001 ) . This effect of gentamicin on nasal potential difference occurred both in patients who were homozygous for stop mutations and in those who were heterozygous , but not in patients who were homozygous for DeltaF508 . After gentamicin treatment , a significant increase in peripheral and surface staining for CFTR was observed in the nasal epithelial cells of patients carrying stop mutations . CONCLUSIONS In patients with cystic fibrosis who have premature stop codons , gentamicin can cause translational " read through , " result ing in the expression of full-length CFTR protein at the apical cell membrane , and thus can correct the typical electrophysiological abnormalities caused by CFTR dysfunction BACKGROUND Respiratory disease in patients with cystic fibrosis is characterized by airway obstruction caused by the accumulation of thick , purulent secretions , which results in recurrent , symptomatic exacerbations . The viscoelasticity of the secretions can be reduced in vitro by recombinant human deoxyribonuclease I ( rhDNase ) , a bioengineered copy of the human enzyme . METHODS We performed a r and omized , double-blind , placebo-controlled study to determine the effects of once-daily and twice-daily administration of rhDNase on exacerbations of respiratory symptoms requiring parenteral antibiotics and on pulmonary function . A total of 968 adults and children with cystic fibrosis were treated for 24 weeks as out patients . RESULTS One or more exacerbations occurred in 27 percent of the patients given placebo , 22 percent of those treated with rhDNase once daily , and 19 percent of those treated with rhDNase twice daily . As compared with placebo , the administration of rhDNase once daily and twice daily reduced the age-adjusted risk of respiratory exacerbations by 28 percent ( P = 0.04 ) and 37 percent ( P < 0.01 ) , respectively . The administration of rhDNase once daily and twice daily improved forced expiratory volume in one second during the study by a mean ( + /- SD ) of 5.8 + /- 0.7 and 5.6 + /- 0.7 percent , respectively . None of the patients had anaphylaxis . Voice alteration and laryngitis were more frequent in the rhDNase-treated patients than in those receiving placebo but were rarely severe and resolved within 21 days of onset . CONCLUSIONS In patients with cystic fibrosis , the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms , result ed in slight improvement in pulmonary function , and was well tolerated RATIONALE Nonsense ( premature stop codon ) mutations in mRNA for the cystic fibrosis transmembrane conductance regulator ( CFTR ) cause cystic fibrosis ( CF ) in approximately 10 % of patients . Ataluren ( PTC124 ) is an oral drug that permits ribosomes to readthrough premature stop codons in mRNA to produce functional protein . OBJECTIVES To evaluate ataluren activity , safety , and pharmacokinetics in children with nonsense mutation CF . METHODS Patients were assessed in two 28-day cycles , comprising 14 days on and 14 days off ataluren . Patients took ataluren three times per day ( morning , midday , and evening ) with r and omization to the order of receiving a lower dose ( 4 , 4 , and 8 mg/kg ) and a higher dose ( 10 , 10 , and 20 mg/kg ) in the two cycles . MEASUREMENTS AND MAIN RESULTS The study enrolled 30 patients ( 16 male and 14 female , ages 6 through 18 yr ) with a nonsense mutation in at least one allele of the CFTR gene , a classical CF phenotype , and abnormal baseline nasal epithelial chloride transport .  Ataluren induced a nasal chloride transport response ( at least a -5-mV improvement ) or hyperpolarization ( value more electrically negative than -5 mV ) in 50 % and 47 % of patients , respectively , with more hyperpolarizations at the higher dose . 
    Output:
    
Participants receiving chronic inhaled tobramycin appeared to have a reduced rate of pulmonary exacerbation compared to those not receiving chronic inhaled tobramycin .
There is currently insufficient evidence to determine the effect of ataluren as a therapy for people with cystic fibrosis with class I mutations .