Genetics, diagnosis and therapy option

Question

Can the new drugs (Vertex) only used with F508del homozygous or would that also be possible with F508del and IVS8T5?

Can one tell exactly from the genes or through a test (e.g. blood) what our son's "protein problem" is?

Many thanks.

Answer

Hello,

the F508del mutation is associated with classic CF and causes an almost complete loss of function of the chloride channel. The T5 mutation, on the other hand, causes only part of the genetic products (chloride channels) to lose their function, whereas the other part remains functional. Therefore, depending on the fraction of functional genetic product, the symptoms are milder than with classic CF where there is no functional genetic product left.

In patients with the T5 allele, the fraction of functional chloride channels varies from patient to patient and from tissue to tissue and can not be predicted based on a genetic test.

VX-809 is a so-called potentiator that is supposed to cause more F508del genetic products to reach the cell membrane, and a combination with VX-770 is supposed to increase the activity of the CFTR ion channel. This means that a therapy combining VX-809 and VX-770 could lead to an improved residual function of the F508del allele, which, together with the varying amount of intact chloride channels in the various tissues, could possibly lead to a sufficient CFTR function. However, these are purely theoretical considerations and only the results of further studies will show if and to which degree these therapeutic approaches are successful.

I hope these explanations answer your question.

Kind regards
Prof. Sabina Gallati

20.11.2012