Human apyrase represents a highly promising therapy to reduce ischemia/reperfusion injury which occurs in10-20% of lung transplant recipients as the consequence of unavoidable processes of procurement, preservation and restoring blood flow. This clinical condition, recently termed primary graft dysfunction, remains an important problem after lung transplantation, and still represents the single biggest cause of early morbidity and mortality for lung recipients. Apyrase strongly inhibits platelet activation and inflammation with modest bleeding risk. Using a protein informatics approach, we have successfully engineered a clot-targeting human apyrase, APT202, which exhibits significantly higher enzymatic activity and platelet inhibition than the wild-type apyrase. With the Phase I SBIR grant support, we will optimize the dose regimen of APT202 that will provide significant benefits while maintaining low bleeding risk in established animal transplantation models. The ultimate goal is to advance APT202 into clinic to improve patient outcome in terms of oxygenation improvement, reduction for duration of mechanical ventilation and hospital stay. Human apyrase represents a highly promising therapy to reduce ischemia/reperfusion injury associated with lung transplantation. We will optimize the dose regimen of a clot- targeting apyrase that will provide significant benefits while maintaining low bleeding risk in established animal transplantation models. ? ? ?
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