Which mutation has more need for therapy?

Question

Dear expert team,

my son (4 years, CF) has the following known mutations: delF508 (inherited by me) and on the other allele R1070Q-S466X. The R1070Q is a missense mutation, the S466X is a nonsense mutation. In case of this rare combination, a marked pancreatic insufficiency has to be expected, and it is like this in my child. The new medications that are investigated, e.g. Kalydeco®, Ataluren® etc. are only suitable for one class of mutations. My question is the following: how can in the future be decided, which of the two (or of all three) mutations has more need for therapy?
I hope my question ist understandable and thank you very much in advance.

Answer

Dear questioner,

in general the CFTR mutations act independetly from each other (another remote example for explanation about non-CF patients at an older age: high blood pressure and diabetes). By this follows: in general, nothing speaks against treating both variants at the same time with a specific molecular therapy for each (again another remote example for explanation: the patients suffering from high blood pressure and diabetes are getting drugs against high blood pressure and diabetes at the same time). However: all medications have side-effects and interactions between pharmacologically active substances have to be known at first.
Here the CF physician is involved, with a profund knowledge of the CFTR activators/ potentiators, in order to decide in the single case, if both mutations can be treated at the same time.
In summary: the question is understandable - the therapeutic effort in case of CF is high enough in daily life and the necessary burden of the oranigsm with pharmacological substances is already high enough, in order to ask, which variant has to be treated first line. However: F508del and S466X are both so-called "severe" (i.e. accompanied by pancreatic insufficiency) mutations, so there is no one less important or more important. In order to find a CF-physician as a specialist in CFTR-therapy, I recommend to ask one of the collegues, who is working in Germany on clinical studies about CFTR-therapeutics
(please find under: muko.info/mukoviszidose-institut/klinische-studien/cf-studien-in-deutschland.html, there: mutation-specific therapies [German site]).

With my best regards, especially for your son,
Frauke Stanke

09.11.2015