DeltaF508/R553X, part II

Question

Dear expert team,

Please allow me a further question concerning the genotype mentioned in the subject line.

In “Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis” (Sermet-Gaudelus I, Boeck KD, Casimir GJ, Vermeulen F, Leal T, Mogenet A, Roussel D, Fritsch J, Hanssens L, Hirawat S, Miller NL, Constantine S, Reha A, Ajayi T, Elfring GL, Miller LL; Am J Respir Crit Care Med. 2010 Nov 15;182(10):1262-72. Epub 2010 Jul 9.), you can find the following graphic summary of the test results: http://171.66.122.149/content/182/10/1262/F3.expansion.html .

Do I have to interpret from the results that DeltaF508/R553X has reacted worse to the treatment with Ataluren and that it is therefore not sure whether the drug shows any effects at all with this gene combination?

Kind regards.

Answer

Dear questioner,

I read the publication you mention and would like to warmly recommend you to not attach too much importance to these data and especially to not draw any conclusions from them for your child.

This study shows preliminary, i.e. only tentative, results for only 30 children who were treated with Ataluren. Among these, only two had the F508del/R553X genotype, and one of these two children reacted positively to the treatment with Ataluren; the other did not show any changes. Furthermore, this study showed only an influence of Ataluren on the nasal epithelium, an improvement of lung function or BMI could not be detected. This means that an effective therapy with this drug is not yet within reach, that more patients have to be tested first and especially that an effect on lung function has to be achieved.

I hope my explanations answered your question.

Kind regards,
Prof. Sabina Gallati

17.04.2012