New drug treatments for cystic fibrosis

When the discovery of the cystic fibrosis gene was announced in October 1989 at a meeting in Tarpon Springs, Florida, the audience gave it a rapturous welcome. We believed this discovery would propel us rapidly towards a cure for a condition that led to death in or before early adulthood. More than 30 years later, we may finally be approaching that goal. It has been a difficult journey.

Cystic fibrosis is a genetic condition. The protein affected by the faulty gene, cystic fibrosis transmembrane conductance regulator (CFTR), is a gated chloride channel present in epithelial cells in airways, sweat glands, the pancreas, and many other organs. More than 350 mutations of the CFTR gene that cause disease have been identified.1 The mutations all reduce the quantity or function of the CFTR protein at the cell surface, though specific actions vary. Some, such as the common F508del mutation, result in no or minimal CFTR function; in others, residual CFTR function is maintained.

The “valley of death,” where promising laboratory observations fail to translate into effective treatments, was particularly challenging for drug development …