New mechanism of Elafin to prevent lung injury in mechanically ventilated newborns

tiakis BIOTECH AG today announced the publication of research results by Alcazar et al. from Stanford University on a new mechanism by which Elafin rescues lung cell survival in the lung of newborn mice subjected to mechanical ventilation. 

Neonatal chronic lung disease or bronchopulmonary dysplasia develops in preterm infants whose lungs are incompletely developed and therefore require respiratory support after birth. The disease condition is characterized by incomplete formation of alveoli, associated with lung cell death and disordered deposition of matrix elastin. Treatment with Elafin is known to mitigate these adverse pulmonary effects of mechanical ventilation with oxygen-rich gas in newborn mice. 

The study identified a novel pro-survival signal which involves the epithelial growth factor receptor (EGFR) and the Protein Klf4. This pro-survival signal is disrupted in the lungs of newborn mice exposed to mechanical ventilation. Elafin treatment reduced cell death in ventilated newborn lungs both by suppressing elastase activity and preserving EGFR-Klf4 signaling. The authors conclude that this could account for Elafin`s benefit in promoting alveologenesis and lung growth in newborn mice during mechanical ventilation. 

These experimental findings coupled with the research group’s observation of significantly increased elastase levels in preterm infants with evolving neonatal chronic lung disease, support the notion that Elafin treatment might be effective in mitigating or preventing neonatal lung injury caused by mechanical ventilation.

Source: Alejandre Alcazar MA, Kaschwich M, Ertsey R, Preuss S, Milla C, Mujahid S, Masumi J, Khan S, Mokres LM, Tian L, Mohr J, Hirani DV, Rabinovitch M, Bland RD. Elafin treatment rescues EGFR-Klf4 signaling and lung cell survival in ventilated newborn mice. Am J Respir Cell Mol Biol. 2018.