PCT 124

Question

Dear expert advice team,

I have the following mutations, 508 and R 1066C.
Since R1066C is a so-called nonsense mutation: Could you inform me if PCT 124 can be a cure in this case or makes treatment more effective?

Is there already a date when this drug will be available?

Thank you very much and kind regards

Answer

Hello,

I am sorry that I have to disappoint you. R1066C is a missense mutation and not a nonsense mutation. PCT 124 is currently being tested with regard to its efficacy. As far as I know it is not foreseeable yet if and when it will be brought to the market as drug. So far the results of the pre-clinical and the clinical studies have been very promising.

PCT 124 is used in patients with a nonsense mutation, since it has been shown that with the help of PCT 124 so-called stop-codons can be ignored and thus an amino acid is integrated into the final protein at the appropriate place.
In the end there is a functional full length CFTR protein.

Normally, nonsense mutations in most cases result in the cell recognizing that the so-called mRNA (the intermediate step in the process from CFTR-gene to the CFTR protein) is defective and therefore it is degraded by the cell.
Without mRNA, however, the CFTR protein cannot be produced. In this case we also say Class 1 mutation (Defective Protein Synthesis).

The situation is different in missense mutations. Here in most cases a CFTR-protein is produced which, however, does not function as well as the normal CFTR. These cases are called Class 4 mutations (Defective Protein Regulation). Probably R1066 C is a Class 4 mutation as well. Thus the therapeutic approach with PTC 124 does not make any sense in connection with R1066 C nor with the F 508del mutation (Class 2, Defective Protein Processing)

With kind regards,
Prof. Stuhrmann-Spangenberg

24.02.2009