Ataluren with stop mutation R1162X

Question

Unfortunately the latest results that were published at the CF congress in Dublin are not really convincing.

I have the following question nevertheless:

Is it true that the R1162X stop mutation is suited very well or at least better than other stop mutations for therapy with Ataluren?

Were any distinctions made between the various stop mutations, and were they also analyzed?

Many thanks for your answer!

Answer

Dear questioner,

We received the following answer from Dr. Jutta Bend of Mukoviszidose e.V., the German CF patient organization:

"You are interested in the effect of Ataluren (=PTC124) with the R1162X mutation. Generally, the data currently available are not reliable enough for concrete statements here.

The results so far (e.g. from a study published in 2012 by Sermet-Gaudelius) suggest that there can be a reaction to Ataluren with various stop mutations (Q493X; G542X; R553X; W882X; E1104X; R1162X; W1282X). However, the case numbers were extremely low, which is why one cannot draw conclusions about a better or worse effect for individual mutations.

As Prof. Tuemmler said in an answer to a similar question in this expert advice, it could be possible that Ataluren works particularly well with R1162X. This is assumed because the R1162X mRNA is produced in the nucleus and is not recognized by the endogenous quality control system at first and therefore a lot of it reaches the ribosome where Ataluren operates.

The Ataluren study was open to patients with any stop mutation. I cannot say at this point whether there has also been a sub-group analysis based on the different mutations, though, because I do not have the data available (they have not been published in their entirety so far).

Only new data can show whether the assumptions made on the basis of lab results can actually be confirmed in studies with humans.

Kind regards
Dr. Jutta Bend"

11.09.2012