Micrometer-scale tPA beads amplify plasmin generation for enhanced thrombolytic therapy

Keith Neeves, Ph.D.
University of Colorado
Denver, CO, U.S.

Current thrombolytic therapies for acute ischemic stroke are limited by slow recanalization, off-target bleeding, and systemic fibrinogen depletion. In this presentation, Keith Neeves introduces a strategy to localize and intensify plasmin activity by covalently linking tPA to micrometer-scale beads. Compared to free tPA, these tPA-beads significantly enhanced local plasmin generation and promoted rapid, self-propagating fibrin degradation in vitro. In a murine stroke model, low-dose 1 µm tPA-beads achieved near-complete cerebral artery recanalization—outperforming a 77-fold higher dose of free tPA. These findings suggest that tPA-beads could improve clot resolution at lower doses, potentially minimizing hemorrhagic risks.