G551D and delta F508 mutations

Question

Hello!

My daughter has the above mutations. Can you say something about progression? Could VX770 help? She is six months old. Would an application be too early at this point?

Answer

The combination of the G551D and delta D508 (F508del) mutations is one of the most common genotypes of CF patients worldwide. On average, this genotype involves a typical CF, although the clinical spectrum of typical CF is actually quite wide, i.e. some patients are affected much less and others much more than the average patient. It is not possible to give a prognosis for individual cases.

The use of VX-770 (a so-called potentiator) is currently being tested in different clinical studies with patients with G551D mutation; one study also involves children (albeit only those six years and older). So far, the results of these studies have been so positive that one can assume that VX-770 is likely to be approved for treatment outside of clinical studies as well in the foreseeable future. It is not known at this point, however, when exactly it will be approved and from what age onwards patients can then be treated with VX-770. At any rate, you should therefore talk about this with the care team at your daughter’s CF centre. The doctors there will learn about the approval as soon as it happens.

VX-770 could also be effective with the F508del mutation, possibly together with a so-called corrector (VX-809 or VX-661). There are clinical studies on this too currently which give reasons to hope that it will be effective as well.

Overall, one can say that your daughter’s genotype is a relatively common one that, on the one hand, is linked to a typical CF; on the other hand, it is exactly this genotype for which clinical studies on the application of so-called mutation class-specific drugs have shown particularly good effects combined with very good toleration. Although these drugs will probably not cure CF completely, one can quite realistically reckon with a significant improvement of the CFTR function (CFTR is the protein – the chloride channel – for which the CFTR gene decodes) and therefore also of the clinical symptoms.

Yours sincerely,
Prof. Stuhrmann-Spangenberg

04.08.2011