Efficacy of VX 770

Question

Dear expert team,
I have besides F508del the mutation "FTR del 2,3".
In case of the homozygous occurence of F508del, one does already know, that VX 770 is efficient only to a very small extent concerning the nasal potential difference.
It is known to me, that there are at the moment no empirical results on the efficacy of VX 770 at the mutation "FTR del 2,3". However, is there any knowledge if more proteins reach the target membrane in case of the mutation "FTR del 2,3" in comparison to F508del (so that also VX 770 could have higher chances to influence the nasal potential difference positively)?
Many greetings

Answer

Hello,
in case of the mutation CFTRdele2,3(21kb) there is a great deletion (loss of a piece of gene) of the exons 2 and 3 of the CFTR-gene, which leads in the end to an early stop-codon in exon 4. Such mutations are in general ascribed to class 1, that means one assumes, that no CFTR is made at all, probably only a very shortended CFTR.
It cannot be assumed that VX 770 can be used successfully in this case. Also Ataluren (PTC124) which is tested in some class 1 mutations at the moment, would probably not be efficient at CFTRdele2,3, as Ataluren is only efficient in case of so-called nonsense-mutations and not in case of so-called frameshift mutations as CFTRdele2,3.

Yours sincerely,
Prof. Manfred Stuhrmann-Spangenberg

01.08.2011