Mutation F508del/E822X

Question

My daughter is six years old and has CF – mutation F508del/E822X. Is there any progress in the treatment of this specific mutation and does it matter if the manifestation of the symptoms of the said mutation is lighter?

Answer

Dear friend,
The E822X mutation, in conjunction to F508del, is associated with pancreatic insufficiency and the typical presentation of the disease. However, please be aware that the individual course of the disease can not be predicted according to the underlying mutations only, as it depends on many other genetic and environmental factors and varies substantially even between patients with the same mutations.
There is progress concerning the radical treatment of CF in patients with the X group mutations. PTC124 is a new, promising drug for the CF patients, who carry the X group mutations (stop mutation/nonsense mutation). Having a nonsense mutation means that the body stops part of the way through making the protein "CFTR". This abnormal protein is responsible for CF. PTC124 causes the body to continue making the protein until a fully functioning "CFTR" is produced. This is the first drug to be studied that could potentially treat the cause of CF and not just the effects of having CF. The effectiveness of PTC124 is however different in individual patients even between those with the exact same mutations. It seems that it depends on individual factors which influence how effective the drug can “ignore the stop codon”. Therefore one can not predict if this drug will be effective in a single patient or not.
There is a study on this particular drug with the title "A Phase 3 Efficacy and Safety Study of PTC124 as an oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis". The trial is a randomised placebo controlled study which means that participants will be randomly allocated to either a group receiving PTC124, or a group receiving a placebo (a dummy medicine with no action). The study consists of 12 months of treatment with a total duration of approximately 14 months. Only around 10% of patients with CF have nonsense mutations and this study plans to recruit 208 participants from a number of countries around the globe. The study was submitted to the Main Research Ethics Committee in May 2009 and following a successful ethics approval, recruitment is due to commence Autumn/ Winter 2009.
At this time it is planned to have sites in a number of European countries but unfortunately not in Greece. However, if a patient from Greece wants to participate, he has to speak English or the language spoken at any of the trial sites well enough to be consented in that langauge. Then he or she might contact that trial site and inquire about participation (see www.clinicaltrials.gov). The decision will be up to the trial site. Please speak also to your local CF Centre if you would like more details on participating in this trial.
Yours friendly
Dr. Stavros Doudounakis

29.12.2009