Novel therapies in the pipeline: Directions of research into platelet inhibition.

BACKGROUND: Ischemic stroke is one of the foremost causes of death and disability in the industrialized world. Apart from both primary and secondary prevention with oral antiplatelet agents, acute treatment is currently limited to recombinant tissue plasminogen activator and interventional therapy. The occurrence of re-thrombosis during and after these interventions clearly indicate the need for further application of novel agents in the treatment of stroke. PLATELET FUNCTION: Current antiplatelet agents in use affect platelet aggregation at different steps. The common limiting factor is the observed occurrence of intracerebral hemorrhage in the setting of acute stroke. PLATELET INHIBITION: Selective inhibition of glycoproteins has been employed already (GP IIb/IIIa inhibitors) but there are other glycoproteins that can be targeted. This is based on research that shows that monoclonal antibody mediated inhibition decreases the burden of disease in mouse models of stroke. A new drug that targets the A1 domain of activated von Willebrand factor that attaches to GP Ib is potentially another way of solving the thrombosis puzzle with the promise that intracerebral hemorrhage would be limited.
CONCLUSION: The continuing search for acceptable levels of platelet inhibition during cerebral ischemic events while minimizing the risk of potentially fatal hemorrhagic side effects is leading the way to selective targeting of the platelet signaling cascade. This raises hope that future therapy will be more effective while having a more favorable safety profile.