THERAPEUTIC TARGETS FOR CYSTIC FIBROSIS

Cystic fibrosis (CF) is a chronic, progressive, autosomal recessive multisystem fatal disease. CF is characterized by many symptoms and complications caused by abnormal anion transport due to dysfunctional CF transmembrane conductance regulator (CFTR) protein. Abnormal CFTR function due to mutations primarily affects the respiratory system and exocrine glands, although the reproductive system is often also involved. Treatment of CF varies depending on the stage of disease, the organs involved and whether the patient suffers from lung infection. Daily baseline therapy attempts to improve mucus clearance, decrease pulmonary inflammation and control infection. More aggressive therapy is required during periods of disease exacerbation. However, ultimately severe pulmonary dysfunction inevitably develops. Double-lung transplantation is a potentially life-saving alternative, although very few patients receive donor organs. To date, therapy for CF includes agents for improving mucociliary clearance and pulmonary inflammation, antibacterial agents and agents for improving CFTR protein function. Thus, the search continues for effective treatments for CF. In recent years, investigators have concentrated on identifying novel targets for therapeutic intervention. This article presents those drug targets that are currently under active investigation for the treatment of CF.