We analyse a paper, which reports an entirely novel approach to the treatment of
cystic fibrosis, consisting in "repairing" the defective
mutant protein. Patients with
cystic fibrosis have a mutation of the gene encoding the
cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial
chloride channel involved in
salt and fluid transport in multiple organs, including the lungs and pancreas. The mutations have different effects on the
CFTR protein, such as misfolding for the ΔF508 mutation (the most common), or defective opening of the
chloride channel for the G551D-CFTR mutation, found in 4 to 5% of the patients. The authors of this work have shown that
VX-770, an agent known previously to increase the activity of wild-type and G551D-CFTR
cell surface protein in vitro, was able, when given orally to 39
cystic fibrosis patients during 14 and 28 days, to partially restore
chloride conductance, as measured by nasal epithelium potential difference. Similarly, the agent partially restored
chloride transport in sweat glands, as measured by the sweat
chloride concentration. Clinically,
VX-770 increased the forced expiratory volume per second (FEVi). Side effects included macular
skin rash, elevation of
blood glucose concentration and
glycosuria. All side effects resolved after discontinuation of the
drug.
VX-770 has also been shown to increase the activity of ΔF508-CFTR channels in vitro, provided they reach the cell surface. This study appears to be a milestone in the treatment of
cystic fibrosis and possibly other
genetic diseases.