Defibrotide: potential for treating endothelial dysfunction related to viral and post-infectious syndromes, 2021, Richardson et al

Defibrotide: potential for treating endothelial dysfunction related to viral and post-infectious syndromes
Edward Richardson, David García-Bernal, Eleonora Calabretta, Rubén Jara, Marta Palomo, Rebecca M Baron, Gregory Yanik, Jawed Fareed, Israel Vlodavsky, Massimo Iacobelli, Maribel Díaz-Ricart, Paul G Richardson, Carmelo Carlo-Stella, Jose M Moraleda

Introduction: Defibrotide (DF) is a polyribonucleotide with antithrombotic, pro-fibrinolytic, and anti-inflammatory effects on endothelium. These effects and the established safety of DF present DF as a strong candidate to treat viral and post-infectious syndromes involving endothelial dysfunction.

Areas covered: We discuss DF and other therapeutic agents that have the potential to target endothelial components of pathogenesis in viral and post-infectious syndromes. We introduce defibrotide (DF), describe its mechanisms of action, and explore its established pleiotropic effects on the endothelium.

We describe the established pathophysiology of Coronavirus Disease 2019 (COVID-19) and highlight the processes specific to COVID-19 potentially modulated by DF. We also present influenza A and viral hemorrhagic fevers, especially those caused by hantavirus, Ebola virus, and dengue virus, as viral syndromes in which DF might serve therapeutic benefit. Finally, we offer our opinion on novel treatment strategies targeting endothelial dysfunction in viral infections and their severe manifestations.

Expert opinion: Given the critical role of endothelial dysfunction in numerous infectious syndromes, in particular COVID-19, therapeutic pharmacology for these conditions should increasingly prioritize endothelial stabilization. Several agents with endothelial protective properties should be further studied as treatments for severe viral infections and vasculitides, especially where other therapeutic modalities have failed.

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See also —

• The importance of endothelial protection: the emerging role of defibrotide in reversing endothelial injury and its sequelae (2021)
• Defibrotide (2016)

 

Sounds potentially useful for the immunothrombotic dysregulation being suggested as part of the long COVID phenotype —

 

Note that when used to rescue hepatic sinusoidal obstruction syndrome / veno-occlusive disease, 2-hour infusions every six hours, for up to 21 days are required. I do not know if there could even be a vague prospect of a low dose IV or alternative parenteral regimen. And of course no-one knows if reversing the hypercoagulable state and endothelial dysfunction would be sufficiently upstream to arrest the disease. It might just start up again under the influence of viral remnants, reactivation etc.

 

I find it hard to take this seriously. Why would a piece like this have 14 authors scattered across the globe if they were not all chums of the people at the biotech startup in Milan (Techitra)?

When you see people justifying a drug using words like 'dysfunction' and then giving 173 different possibly relevant pathways it is time to be sceptical. Effective drugs are justified by hard data relating to a single mechanism on the whole.

The existence of a journal called expert opinion in therapeutic targets is a bit of joke anyway.

 

See also in vitro study in acute covid and thrombotic microangiopathies: Defibrotide mitigates endothelial cell injury induced by plasmas from patients with COVID-19 and related vasculopathies (2023, Thrombosis Research)