THERAPIES FOR NEONATAL DISEASES OF THE SURFACTANT SYSTEM

A critical adaptation required for successful extrauterine life is the onset of respiration. The production of pulmonary surfactant by alveolar type II (AT2) cells is required for functional ventilation. Pulmonary surfactant is produced in lamellar bodies in AT2 cells. Key components of pulmonary surfactant include phospholipids and surfactant proteins B (SP-B) and C (SP-C). Phospholipids are transported into lamellar bodies by ATP-binding cassette subfamily A member 3 (ABCA3) where they combine with SP-B and -C to form surfactant that is secreted into alveoli. Recessive loss of function mutations in surfactant protein B (SFTPB) and ABCA3, or monoallelic dominant mutations in surfactant protein C (SFTPC), can cause severe respiratory distress in term newborns, later-onset childhood interstitial lung disease (ChILD), or adult-onset ILD. Currently, no specific treatments for these diseases are available. Genetic therapies, including gene addition and gene editing strategies, offer the possibility to correct these defects in AT2 progenitor cells.