Information on PTC-124

Question

Hello,
I have read with great interest the question of a father of two CF children in Austria.
In this question, the study drug PTC124 was mentioned. Could you please provide more information on this interesting medication and scientific approach? My daughter (28yr) suffers from CF, which was shown to be caused by a homozygous deltaF508 mutation.

Thank you for your answer,
E. Böger

Answer

Dear E. Böger,

Since the CF gene was discovered in 1989, it became evident that the well described CF-phenotype is caused by a rather large number (>1500) of different genetic mutations. Research and development today is aiming to tailor drugs for specific treatment of the underlying genetic defect. As you mention, your daughter was diagnosed with a homozygous deltaF508 mutation in the CF gene. This mutation belongs to class II of a currently accepted classification of CF genetic defects. However, substance PTC 124 was specifically designed for treatment of patients with a class I mutation (so called stop-mutation; e.g., R553X). Therefore, in patients with class II mutations, such as your daughter, no beneficial effect of the drug is to be expected

For your information:
Class I mutations cause a premature abort of the ribosomal translation. The consequence is unstable, shortened or abrogated protein synthesis. The substance PTC 124 was shown to prevent the premature termination of the protein-biosynthesis in the ribosome. There is evidence that an increase of CFTR (main product of the CF-gene) synthesis to as little as 5% can result in a relevant increase of ion transport function in the cell membrane (literature recommendation: Hirche et al., New concepts of Pathosphysiology and Therapy in Cystic Fibrosis, Pneumologie 2005; German only)

Best wishes,
TO Hirche

15.01.2009