
The study reveals that while lumacaftor improves F508del CFTR processing, it paradoxically inhibits its channel activity. Real-time assays and patch-clamp data show reduced open probability and forskolin-induced currents in CFBE-DF and HEK-DF cells. Unlike tezacaftor or elexacaftor, lumacaftor disrupts functional rescue at 37°C, possibly explaining Orkambi’s modest clinical performance.
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