Composite CFTR heterozygote

Question

Hello,
We are the parents of an 11 years old CF boy. He has 2 different CFTR mutations from class II and I respectively: F508del and 1717-1G>A. If a treatment like the Vx809 is efficient for the F508del mutation, could our child be “cured”? Would it be necessary to add another treatment for the other mutation? In summary: is it necessary to treat the 2 mutations or treating one is enough? Thank you for your answer.

Answer

Novel therapies have recently emerged in cystic fibrosis targeting the defective CFTR protein. Several molecules are currently studied to correct the effects of specific CFTR mutation classes (protein therapies). Vx809 (Vertex) is a CFTR corrector that targets the class II CFTR mutations (F508del). Clinical trials evaluating efficacy of this molecule are underway and have concerned so far homozygous F508del patients (patients with 2 F508del mutations). Promising results have been shown for this therapy. It was well tolerated and allowed normalization of the chloride secretion; analyses of other clinical parameters are underway.
As your son has one F508del mutation, he may benefit from this type of therapy. It has indeed been shown that the rescue of only a partial amount of CFTR was enough to restore a sufficient function. The clinical trials have concerned so far only patients with 2 F508del mutations but new trials would certainly target patients with other mutations. We have to stay careful before talking of “complete recovery” as these trials are not finalized. Anyway, the clinical trials of such target-protein therapies have very encouraging results! I hope to have answered your questions. Regards,
Harriet Corvol

28.03.2011