Recombinant CC10 for treatment of meconium aspiration

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DESCRIPTION (provided by applicant): Recombinant human CC 10 is a novel therapeutic agent that is currently in clinical development for prevention of bronchopulmonary dysplasia (BPD) in preterm infants. CC10 is also known as clara cell secretory protein (CCSP) or uteroglobin and is produced primarily by tracheal and bronchial epithelia. The protein appears to have potent anti-inflammatory properties, one of which is inhibition of secretory phospholipase-2 (sPLA2). Several studies in CC10-deficient mice indicate that CC10 is very important in developing and maintaining normal lung function. Endogenous CC 10 is deficient in the lungs of preterm infants such that rhCC 10 is currently being administered as a replacement, analogous to exogenous surfactant in premature infants with respiratory distress syndrome (RDS). Other lung pathology may also be ameliorated by the introduction of rhCC10 into the lung. In term infants, the aspiration of meconium into the airway (either in utero or immediately after birth) causes acute lung injury, characterized by surfactant inactivation, atelectasis and pulmonary inflammation, sPLA2 is present in meconium and is thought to play a significant role in the pathogenesis of the injury process. While surfactant replacement therapy has been used in the treatment of meconium aspiration syndrome (MAS), often the pulmonary inflammatory response is so fulminant that this therapy is ineffective in treating the acute lung injury (possibly due to inactivation of the exogenous surfactant). Since rhCC 10 is an anti-inflammatory agent with known ability to inhibit sPLA2, we propose to verify the ability of rhCC 10 to inhibit sPLA2 activity in meconium (in vitro) and to test its efficacy in an animal model of MAS in newborn piglets (in vivo).