Fixing Function In Cystic Fibrosis

By helping a defective protein reach its destination, researchers have restored some function to lung cells from patients with cystic fibrosis (Nat. Chem. Biol., DOI: 10.1038/nchembio.275). The approach might lead to new CF treatments.

Most patients with CF have a mutation in a chloride ion-channel protein that keeps it from assuming its functional location in the cell membrane. Rather than targeting the faulty channel directly, a team led by William E. Balch of Scripps Research Institute instead focused on protein-processing machinery.

With small molecules, the team blocked histone deacetylase enzymes, which influence gene expression and other events by removing acetyl groups from lysine side chains. In lung cells from CF patients, low doses of one inhibitor, suberoylanilide hydroxamic acid (SAHA), already an FDA-approved drug for cancer, gradually restored about 28% of normal channel function and kept it there for up to 10 days after treatment. The team suggests that the inhibitors shape protein processing by modifying chromatin, which stops cells from treating the channel as a defective intruder. They are still working out the mechanism.