Inhibiting the Inhibitor: Would Targeting Pai-1 Result in a Low-dose, Well-tolerated Treatment of Empyema?
Year: 2025
Type: article
Abstract: infectious pleural injury. Anti-PAI-1 monoclonal antibodies (mAbs) and a short Docking Site Peptide (DSP), which affect the PAI-1 mechanism differently, were first tested in a rabbit model of chemically-induced pleural injury. Modulating different steps of the PAI-1 mechanism resulted in an up to eight-fold increase in the efficacy of exogenous fibrinolysins. DSP, subsequently tested in a rabbit model of empyema, increased the efficacy of sctPA in both early- and advanced-stage empyema by at least eight and four-fold, respectively. While small-molecule PAI-1 inhibitors are under investigation, there is currently no FDA-approved PAI-1-targeted treatment. We believe that DSP and phage-display selected peptides that compete with mAbs for PAI-1 will be well-tolerated, tractable in clinical settings, and address both pleural fibrosis and thickening with minimal off-target effects. The results support our hypothesis and objective to develop a novel, cost-effective, low-dose pharmacological intervention for empyema suitable for patients who are at elevated risk for surgery or conventional fibrinolytic therapy.
Source: PubMed
Institutions: The University of Texas at Tyler, KU Leuven
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Delivery of PAI-1-targeted intrapleural fibrinolytic therapy for empyema, Optimization of a Rabbit Retained Hemothorax Model for Evidence-Based Pharmacologic Interventions, Concurrent targeting of inflammation and the inhibition of the fibrinolytic system to increase the efficacy of empyema treatment
OpenAlex ID: W7163449585