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Fibrinolytic Therapy for Acute Lung Injury: The Case for Inhaled Tissue Plasminogen Activator (tPA)

Stringer KA.

RDD Europe 2009. Volume 1, 2009: 25-34.

Abstract:

Presently, there is no effective pharmacotherapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) although the contribution and relationship between inflammation, and the coagulation and fibrinolytic systems have now been appreciated. This improved understanding has led to the identification of new and potentially novel therapeutic targets. We have previously demonstrated that, in addition to its fibrinolytic function, tissue plasminogen activator (tPA) possesses anti-inflammatory activity. These two properties could be particularly useful in the treatment of ALI/ARDS in which loss of fibrinolytic homeostasis and oxidant stress combine to produce lung injury. Results from work in mice testing a pulmonary formulation of tPA (pf-tPA) targeted to the site of action in the lungs appears to show that pf-tPA is safe and efficacious following repeat administration in healthy animals and in an experimental of ALI/ARDS, respectively. However, the drug’s local clearance from the lungs remains to be determined. These data provide the basis for continued study of pf-tPA as a therapeutic strategy for the clinical management of ALI/ARDS.