Cystic fibrosis (CF) is an autosomal recessive genetic disorder affecting approximately 75,000 individuals worldwide, which is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The disease affects multiple organ systems including the lungs and respiratory tract, pancreas, intestine, liver and kidneys. However, the highest medical need is in the lungs, where complications from CF-related lung disease currently account for 80% of all CF deaths.
CF lung disease is hallmarked by dehydration of the fluid volume on the airway surface, resulting in reduced clearance of mucus, the lung’s principle mechanism for cleansing itself. The mucus becomes thick and sticky, progressively accumulating into obstructions that are chronically colonized by viruses and bacteria, leading to frequent, acute lung infections, inflammation and loss of lung function. The long-term result of the constant insult from the infections and the body’s own immune response is progressive, permanent tissue damage and scarring (fibrosis) in the lung that commonly requires lung transplantation and often leads to early death. No cure for cystic fibrosis is known, although several therapies have been approved to address the underlying cause of the disease in some patients. Despite these therapies, the median age of survival for CF patients is only 30-40 years of age.