medicines (small molecules)

Question

I try to find medicines or research projects for possible medication for class V and VI mutations. For class V mutations, the mRNA splicing does not work properly or the transcription level is too low, as for class VI mutations, there is not enough CFTR channel in the membrane because the increased turnover of the protein from this mutation. It seems I can’t find information whether there has been an attempt to make specific small molecules (mutation-specific medicine). Is that right or didn’t I find it?

Answer

Dear questioner,
Generally, your information is correct. There is indeed at present little research for class V and VI CFTR mutations.
There is one pilot study that may interest you (NCT01685801 on www.clinicaltrials.gov). This is a single-center study in Denver in which a patient with a known genotype with residual function is used as his own control. This is a "new" method of research in which the improvement after a treatment of two weeks is compared with the baseline values of the same patient. Patients with very specific mutations are included in this study such as A455E, 3849 +10 KBC and D1152H, all examples of class V mutations).

Since patients with class V and VI mutations have residual CFTR function, we expect that ivacaftor can bring a clinical improvement. For residual function mutations, improvement with ivacaftor has been proven in vitro. The pilot study mentioned is the first attempt to prove also a clinical benefit in patients. As many of these mutations are very rare, the strategy chosen has been a pilot project with the patient as his own control.
Prof. K. de Boeck

14.10.2013