HUMAN LUNG SURFACTANT DEFICIENCY^DIAGNOSIS AND THERAPY

THIS PROPOSAL DESCRIBES THE DEVELOPMENT OF A MODERN DIAGNOSTIC TEST AND THERAPY FOR INFANT RESPIRATORY DISTRESS SYNDROME (RDS). RDS IS THE LEADING CAUSE OF NEONATE MORTALITY AND MORBIDITY. IT IS DUE TO INADEQUATE LEVELS OF LUNG SURFACTANT, A LIPID-PROTEIN COMPLEX ESSENTIAL FOR LUNG INFLATION. CURRENT DIAGNOSTIC ASSAYS ARE BASED ON THE LIPID COMPONENT OF SURFACTANT AND ARE UNRELIABLE. WE PROPOSE TO DEVELOP A SENSITIVE AND ACCURATE ENZYME-LINKED IMMUNOADSORBENT ASSAY DIRECTED AGAINST THE MAJOR PROTEIN COMPONENT OF SURFACTANT. RDS IS NOW TREATED WITH A RESPIRATOR UNTIL SURFACTANT DEVELOPS, YET THIS OFTEN LEADS TO LUNG DISORDERS. NATURAL SURFACTANT HAS BEEN SUCCESSFULLY ADMINISTERED AS A THERAPY BUT LIMITED AVAILABILITY MAKES THIS APPROACH IMPRACTICABLE FOR ROUTINE THERAPY. RECOMBINANT DNA TECHNOLOGY WILL BE USED TO PRODUCE THE NEEDED SURFACTANT PROTEIN. THE HUMAN GENE ENCODING THE PROTEIN WILL BE CLONED AND EXPRESSED, AND THE APOPROTEIN CONSTITUTED WITH LIPIDS TO PROVIDE A SAFE AND EFFECTIVE THERAPY.