Genotype F508del/1717-1G>A and clinical trial

Question

Hello,
First thank you for your site and your answers!
Here's what I read in the search results. "Currently, four Phase 3 studies are underway for VX-661 (100 mg once daily) in combination with ivacaftor (150 mg every 12 hours). One of those studies is in people with two copies of the F508del mutation. The other three studies will enroll people with cystic fibrosis who have one copy of the F508del mutation and a second mutation that is either a gating mutation, residual function mutation or a mutation that results in minimal CFTR function".
So my question is this: as being compound heterozygous with the mutations delF508 and 1717-1G>A, could I possibly be part of this test?
In advance thank you for your reply.
Yours

Answer

Hello,
The 1717-1G> A mutation is a class I stop mutation: it results in stopping the synthesis of the CFTR protein and its destruction in the cell nucleus. The truncated and destroyed protein can therefore not reach the cell membrane an operate there as a chloride channel.
This mutation is therefore not part of the mutations resulting in a minimal function of the CFTR protein. You do not have the criteria for inclusion in clinical trials involving VX-770 (ivacaftor) and VX-661 molecules.
By cons, a clinical study of PTC Therapeutics Laboratory which currently begins in France includes compound heterozygous patients associating F508del mutation and a stop mutation which includes the mutation 1717-1G> A.
More information can be found by clicking on the following link which returns to a previous answer ECORN-CF:
ecorn-cf.eu/index.php?id=65&tx_expertadvice_pi1%5Bshowitem%5D=3324&tx_expertadvice_pi1%5Bsearch%5D=


Hope this answer can help.
Best wishes

Gilles RAULT, MD, Roscoff CF Center

06.04.2015