ABC subfamily (ATP-binding cassette) A member 3 (ABCA3) is a lipid transporter found in the limiting membrane of lamellar bodies and expressed in alveolar type II cells. It is necessary for surfactant storage and equilibrium in the lungs. The most prevalent genetic cause of respiratory distress syndrome in mature babies and interstitial lung disease in children is mutations in the ABCA3 gene. There is no cure for lung cancer other than lung transplantation. To address the lack of causative treatment options for ABCA3 deficiency, a fast and dependable method for investigating variant-specific molecular processes and identifying pharmacological modulators for mono- or combination therapy is required.

To that end, the researchers created a phenotypic cell-based assay that uses machine-learning algorithms to recognize morphological differences in WT and mutant cells to identify ABCA3 wild-type-like or mutant-like cells autonomously. The assay was then used to find new therapeutic candidates for ABCA3 specific molecular correction by a high-content screening of 1,280 FDA-approved small compounds. Cyclosporin A (CsA) has been identified as a strong corrector selective for some ABCA3 mutations but not all. The previously established functional small format assays were used to confirm the results. As a result, CsA may be chosen for orphan drug screening in patients in controlled repurposing trials.