Gene Therapy for Surfactant Disorders

At birth, some babies fail to breathe due to a failure to inflate their lungs and often this is due to genetic diseases resulting in a lack of surfactant protein. Surfactant forms a thin film that covers the gas exchange surface in the lung. It is required to prevent the lung from collapse. Several proteins are crucial to normal surfactant metabolism, for example, surfactant protein B, surfactant protein C and ABCA3. Absence or reduced function of such proteins due to genetic mutation leads to severe respiratory distress. The outlook for affected babies can be poor and progress in developing treatments has been slow as the majority of such diseases are very rare. In my DPhil project I am investigating gene therapy for surfactant disorders. The principle is to deliver the correct genetic information to specific cells in the lung called alveolar type II cells, the site of surfactant metabolism, using adeno-associated virus (AAV) as a vehicle for delivery. AAV is a non-pathogenic virus which is known for its ability to infect different target tissues with a good safety profile in gene therapy applications. If the delivered genes are expressed long-term in the lung this approach has the potential to treat surfactant disorders. Importantly, even partial correction may have a benefit, for example by extending the window in which lung transplantation could be offered.