F508del Heterozygous

Question

Hello,
I read this article very encouraging:
http://www.news-medical.net/news/20150519/Two-drug-combination-improves-lung-function-in-some-cystic-fibrosis-patients.aspx
But for heterozygous F508del, do not we say that if we correct a mutation, we "cure" the disease ??
So, those who have at least one F508del mutation, they are not as concerned ??
In advance thank you for your reply
Best Regards

Answer

Hello,

The article you are referring to reports the results of a clinical study involving a potentiator (ivacaftor) and a corrector (lumacaftor) in homozygous F508del patients. The observed effect is indeed statistically significant although clinically modest: it is the result adding the effect of this combination on each of both F508del mutations. The result of this study justified an application for marketing authorization with a strictly limited indication for homozygous F508del patients.

For CF patients having 2 different mutations (compound heterozygous) one of which is a F508del, access to treatment by modulators (potentiator and / or corrector) depends on the nature of the other mutation. To date, if the other associated mutation F508del is a class III mutation (G551D, G178R, G551S, G1244E, G1349D, S1251N, S1255P, S549N or S549R), these patients may benefit from treatment with ivacaftor unless special contraindications.

Nevertheless the effects of these modulators for encouraging they are, cannot be considered as a cure because these modulators:
- do not sufficiently restore CFTR function to correct the malfunction;
- have effect as long as the treatment is continued;
- cannot correct the irreversible damage;
- are not without side effects that can sometimes require discontinuation of treatment.

Hope this answer can help.
Best wishes
Gilles RAULT, MD, Roscoff CF Center

05.08.2015