Alan Nurden: Safer Antithrombotic Therapy Through GPVI
Alan Nurden, Emeritus Research Director at CNRS, Co-Founder of the French National Reference Centre for Inherited Platelet Disorders (CRPP), shared a post on LinkedIn about a recent article by Stefano Navarro et al. published in Signal Transduction and Targeted Therapy, adding:
“Targeting GPVI in anti-thrombotic therapy
The absence of significant bleeding in patients deficient in the platelet collagen receptor GPVI makes this receptor an attractive target for anti-thrombotic therapy.
Results from several mouse models also point in this direction.
However, initial results from studies on the use of antibody-based therapies have been mixed and disappointing.
Now, in this article from the group led by Bernhard Nieswandt in the University of Wuerzburg, the authors present a carefully thought-out evaluation of the ways that GPVI can be targeted in clinic.
Using different mouse models, they show that monoclonal antibody-induced stripping of GPVI from the platelet surface in the liver sinusoids provides a more effective and longer inhibition than the short-term blocking of GPVI function by monoclonal antibody Fab fragments.
At the same time, hemostasis is maintained. Strikingly, they also show that pharmacologic downregulation of GPVI from platelets does not have to be complete to assure anti-thrombotic protection.
This re-opens the case for anti-GPVI therapy not only for ischemic stroke and arterial thrombosis but also in a wider perspective for thrombo-inflammation. This article is highly recommended and congratulations to the authors.”
Title: Partial downregulation of platelet glycoprotein VI by low affinity antibodies confers sustained and safe antithrombotic protection
Authors: Stefano Navarro, Sarah Beck, Sabrina I. Bonfiglio, Ernesto J. Cuenca-Zamora, Lukas J. Weiß, Marijke Kuijpers, Johan Heemskerk, David Stegner, Bernhard Nieswandt
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