Heterozygous F508del/2789+5G>A

Question

Hello, I am 56 years old and CF compound heterozygous F508del / 2789 + 5G> A. I read several foreign sites that ivacaftor was prescribed to patients with the same mutations than me, with results that seem spectacular.
My pancreas hardly works, but being still pre-diabetic I try to save the few that still works !! Also thank you for getting more information and telling me if this medication applies for my second mutation in different countries, and also how to try to save some of my pancreas, if I can take this drug in France with derogation if needed and if no contra-indications! The time is particularly counted, my pancreas will be completely destroyed before the other medications do exist, it is clear. And to be quite diabetic is harder to live than what I already know. Thank you for understanding. Also instructive reading for all those who help us much.
Regards.

Answer

Hello,

The mutation 2789 + 5G>A is a class V mutation, say encoding the synthesis of a protein migrating well until the membrane, functional but produced in small quantities.

This is a rare mutation, found in 521 of over 40 000 CF patients registered in the CFTR2 international database.

The treatment with ivacaftor and lumacaftor is actually available only for homozygous F508del patients. I am not aware of publications reporting results in patients with other mutations.
Regarding ivacaftor, given the results of clinical trials, it may be prescribed, unless otherwise contrindication, for patients with at least one of the following Class III mutations: G551D, G178R, G551S, G1244E, G1349D, S1251N, S1255P, or S549N S549R.

Apart from these situations, indications called "compassionate" can be made sparingly so, case by case and according to highly formalized procedure including the agreement of the lab owner of the product.

Furthermore, if the expected benefit of these treatments is mainly respiratory, some recent publications on patients under this indication show a better functioning of pancreatic cells producing insulin. I am not aware that this work has led to clinical trials focused on pancreatic exocrine function (secretion of pancreatic enzymes) and endocrine (secretion of insulin and glucagon).

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

05.08.2015