Defibrotide: potential for treating endothelial dysfunction related to viral and post-infectious syndromes
Por:
Richardson, E, Garcia-Bernal, D, Calabretta, E, Jara, R, Palomo, M, Baron, RM, Yanik, G, Fareed, J, Vlodavsky, I, Iacobelli, M, Diaz-Ricart, M, Richardson, PG, Carlo-Stella, C and Moraleda, JM
Publicada:
3 jun 2021
Ahead of Print:
1 jun 2021
Resumen:
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.
Filiaciones:
Richardson, E:
Quinnipiac Univ, Frank H Netter MD Sch Med, North Haven, CT USA
Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA
Garcia-Bernal, D:
Univ Murcia, Virgen Arrixaca Univ Hosp, Stem Cell Transplant & Cell Therapy Unit, Dept Med,IMIB Arrixaca, Murcia, Spain
Calabretta, E:
Humanitas Univ, Dept Biomed Sci, Rozzano Milano, Italy
IRCCS Humanitas Res Hosp, Dept Oncol & Hematol, Rozzano Milano, Italy
Jara, R:
Univ Murcia, Virgen Arrixaca Univ Hosp, Intens Care Unit, Murcia, Spain
:
Univ Barcelona, Hosp Clin, Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Barcelona Endothelium Team, Barcelona, Spain
Baron, RM:
Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA
Yanik, G:
Univ Michigan, Dept Pediat, Blood & Marrow Transplantat Program, Ann Arbor, MI 48109 USA
Univ Michigan, Dept Internal Med, Blood & Marrow Transplantat Program, Ann Arbor, MI 48109 USA
Fareed, J:
Loyola Univ, Med Ctr, Dept Mol Pharmacol & Therapeut, Hemostasis & Thrombosis Res Labs, Chicago, IL 60611 USA
Vlodavsky, I:
Technion, Rappaport Fac Med, Technion Integrated Canc Ctr, Haifa, Israel
Iacobelli, M:
Techitra Srl, Milan, Italy
Diaz-Ricart, M:
Barcelona Endothelium Team, Barcelona, Spain
Hosp Clin Barcelona, CDB, Pathol Dept, Hematopathol, Barcelona, Spain
IDIBAPS, Barcelona, Spain
Richardson, PG:
Quinnipiac Univ, Frank H Netter MD Sch Med, North Haven, CT USA
Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA
Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancy, Boston, MA 02115 USA
Carlo-Stella, C:
Quinnipiac Univ, Frank H Netter MD Sch Med, North Haven, CT USA
Humanitas Univ, Dept Biomed Sci, Rozzano Milano, Italy
IRCCS Humanitas Res Hosp, Dept Oncol & Hematol, Rozzano Milano, Italy
Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA
Moraleda, JM:
Univ Murcia, Virgen Arrixaca Univ Hosp, Stem Cell Transplant & Cell Therapy Unit, Dept Med,IMIB Arrixaca, Murcia, Spain
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