OC 22.3 - Effects of platelet-inspired haemostatic nanoparticles on bleeding in von Willebrand disease murine models

Sunday, July 10, 2022

3:15 PM – 3:30 PM

Location: ExCel Center, S11B

Presentation Format: In-Person

Presenting Author(s)

Stéphanie Roullet, MD PhD

Researcher
Inserm U1176 - HITh
Le Kremlin-Bicêtre, Ile-de-France, France

Co-Author(s)

NL

Norman Luc

PhD student
Case Western Reserve University
Cleveland, Ohio, United States
JR

Julie Rayes

Researcher
University of Birmingham
Birmingham, England, United Kingdom
FA

Frédéric Adam

Researcher
Inserm
Le Kremlin-Bicêtre, Ile-de-France, France
AD

Andrew Ditto

Director of Research and Development
Haima Therapeutics
Cleveland, Ohio, United States
EG

Emily Gahagan

Research Scientist
Haima Therapeutics
Cleveland, Ohio, United States
CP

Christa Pawlowski

COO
Haima Therapeutics
Cleveland, Ohio, United States
MB

Michael Bruckman

CEO
Haima Therapeutics
Cleveland, Ohio, United States
Peter J. Lenting, PhD

Principal Investigator, Director of research
Laboratory for Hemostasis, Inflammation and Thrombosis, Unité Mixte de Recherche S1176, Institut National de la Santé et de la Recherche Médicale, Université Paris-Saclay, Le Kremlin-Bicêtre, France
Paris, Ile-de-France, France
AS

Anirban Sen Gupta, PhD

Professor of Biomedical Engineering
Case Western Reserve University
Cleveland, Ohio, United States
Cécile V. Denis, PhD

Principal investigator, Director of Research
Laboratory for Hemostasis, Inflammation and Thrombosis, Unité Mixte de Recherche S1176, Institut National de la Santé et de la Recherche Médicale, Université Paris-Saclay, Le Kremlin-Bicêtre, France
Le Kremlin-Bicêtre, Ile-de-France, France

Background: Platelet-inspired nanoparticles that emulate platelet’s injury site-specific adhesion and aggregation functions via surface-decoration with three biofunctional peptides (von Willebrand factor (VWF)/phospholipid-binding peptides (VBP), collagen-binding peptides (CBP) and fibrinogen-mimetic peptides (FMP), have shown haemostatic efficiency in pre-clinical models of thrombocytopenia and trauma. Therefore, it was investigated whether such nanoparticles could be beneficial in the treatment of von Willebrand disease (VWD).

Aims: To assess haemostatic efficacy of platelet-inspired nanoparticles in VWF-KO and VWD-type 2B mice following tail-clip injury.

Methods: VWF-KO and VWD-type 2B mice received 2 mg/kg of different nanoparticle formulations: undecorated (control), single, double or triple peptide-decorated (VBP and/or CBP and/or FMP). Ten minutes post-injection, 3 mm of the tail tip was amputated and blood was collected over 20 min for VWF-KO mice and 30 min for VWD-type 2B mice. Quantitative data (mean±SD) were compared with ANOVA and Tukey’s multiple comparisons test.

Results: In VWF-KO mice, triple peptide-decorated particles significantly reduced bleeding compared to control particles (183±174 µL vs 539±203 µL; p< 0.0001) and not statistically different than wild-type mice (19±18 µL; p=0.2043). Here, single or double peptide-decorated particles did not significantly reduce bleeding. In VWD-type 2B mice, bleeding was significantly reduced with triple peptide-decorated particles compared to control particles (631±206 µL vs 966±199 µL, p=0.0001) and with two combinations of double peptide-decorated particles compared to control particles (587±271 µL with CBP+VBP, p=0.0003; 568±286 µL with CBP+FMP, p< 0.0001). Double peptide-decorated particles with VBP+FMP or single peptide-decorated particles did not affect bleeding.

Conclusion(s): Platelet-inspired biosynthetic nanoparticles significantly reduced bleeding in VWD murine models. In VWD-type 2B mice, the importance of the CBP-decoration highlights the pivotal role of collagen in particle anchoring and action. In VWF KO mice, all 3 peptides were required to achieve haemostatic efficiency. These results warrant further investigation of platelet-inspired nanoparticles as a novel strategy for the haemostatic management of VWD.