394delTT and Ataluren (PTC124)

Question

My two children (aged 6 months and 2.5 years old) have cystic fibrosis and one of their mutations is the class I frameshift mutation 394delTT (a.k.a., the scandinavian mutation). 394delTT encodes a stop codon in exon 4.

Answer

Dear Questioner
Ataluren, previously known as PTC124, is a novel agent which is effective in overcoming premature stop codons in the generation of functional CFTR. We know that it is not effective with all stop mutations, and to date it has been studied solely in those individuals with CF caused by nonsense mutations. Initial results from phase 2 clinical trials have indicated that ataluren resulted in production of CFTR protein and significant improvements in chloride channel function. Ataluren therapy was associated with significant reductions in cough frequency and there was a trend towards an improvement in lung function.[1] There have not been any studies specifically for class 1 frameshift mutations, and so at present it is not known if ataluren would be effective for these particular individuals as well.

1. www.ptcbio.com/ataluren/


Best regards
Dr David Cromer

09.07.2012