scholarly journals The thrombopoietin receptor agonist eltrombopag inhibits human cytomegalovirus replication via iron chelation

2019 ◽  
Author(s):  
Jens-Uwe Vogel ◽  
Sophie Schmidt ◽  
Daniel Schmidt ◽  
Florian Rothweiler ◽  
Benjamin Koch ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Receptor Agonist ◽  
Iron Chelation ◽  
Haematopoietic Stem Cell ◽  
Drug Resistant ◽  
Thrombopoietin Receptor ◽  
Hcmv Disease ◽  
Adult Mesenchymal Stem Cells ◽  
Thrombopoietin Receptor Agonist ◽  
Hcmv Replication

AbstractThe thrombopoietin receptor agonist eltrombopag was successfully used against human cytomegalovirus (HCMV)-associated thrombocytopenia refractory to immunomodulatory and antiviral drugs. These effects were ascribed to effects of eltrombopag on megakaryocytes. Here, we tested whether eltrombopag may also exert direct antiviral effects. Therapeutic eltrombopag concentrations inhibited HCMV replication in human fibroblasts and adult mesenchymal stem cells infected with six different virus strains and drug-resistant clinical isolates. Eltrombopag also synergistically increased the anti-HCMV activity of the mainstay drug ganciclovir. Time-of-addition experiments suggested that eltrombopag interferes with HCMV replication after virus entry. Eltrombopag was effective in thrombopoietin receptor-negative cells, and addition of Fe3+ prevented the anti-HCMV effects, indicating that it inhibits HCMV replication via iron chelation. This may be of particular interest for the treatment of cytopenias after haematopoietic stem cell transplantation, as HCMV reactivation is a major reason for transplantation failure. Since therapeutic eltrombopag concentrations are effective against drug-resistant viruses and synergistically increase the effects of ganciclovir, eltrombopag is also a drug repurposing candidate for the treatment of therapy-refractory HCMV disease.

scholarly journals The Thrombopoietin Receptor Agonist Eltrombopag Inhibits Human Cytomegalovirus Replication Via Iron Chelation

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 31 ◽  
Author(s):  
Jens-Uwe Vogel ◽  
Sophie Schmidt ◽  
Daniel Schmidt ◽  
Florian Rothweiler ◽  
Benjamin Koch ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Receptor Agonist ◽  
Iron Chelation ◽  
Drug Resistant ◽  
Hematopoietic Stem ◽  
Thrombopoietin Receptor ◽  
Hcmv Disease ◽  
Adult Mesenchymal Stem Cells ◽  
Thrombopoietin Receptor Agonist ◽  
Hcmv Replication

The thrombopoietin receptor agonist eltrombopag was successfully used against human cytomegalovirus (HCMV)-associated thrombocytopenia refractory to immunomodulatory and antiviral drugs. These effects were ascribed to the effects of eltrombopag on megakaryocytes. Here, we tested whether eltrombopag may also exert direct antiviral effects. Therapeutic eltrombopag concentrations inhibited HCMV replication in human fibroblasts and adult mesenchymal stem cells infected with six different virus strains and drug-resistant clinical isolates. Eltrombopag also synergistically increased the anti-HCMV activity of the mainstay drug ganciclovir. Time-of-addition experiments suggested that eltrombopag interfered with HCMV replication after virus entry. Eltrombopag was effective in thrombopoietin receptor-negative cells, and the addition of Fe3+ prevented the anti-HCMV effects, indicating that it inhibits HCMV replication via iron chelation. This may be of particular interest for the treatment of cytopenias after hematopoietic stem cell transplantation, as HCMV reactivation is a major reason for transplantation failure. Since therapeutic eltrombopag concentrations are effective against drug-resistant viruses, and synergistically increase the effects of ganciclovir, eltrombopag is also a drug-repurposing candidate for the treatment of therapy-refractory HCMV disease.

Quality of Life Improvements Following Eltrombopag Treatment in Children with Chronic Immune Thrombocytopenia: Case Report

2021 ◽  
Vol 104 (4) ◽  
pp. 672-675
Keyword(s):  
Quality Of Life ◽  
Platelet Count ◽  
Receptor Agonist ◽  
Immune Thrombocytopenia ◽  
Case Series ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Low Platelet Count ◽  
Chronic Immune Thrombocytopenia

The present case series described six chronic immune thrombocytopenia patients (cITP), with a median age of 7.7 (7.0 to 13.0) years and low platelet count at 15,500 (7,000 to 20,000)/uL. They were suffering from bleeding symptoms and side effects of treatment. After enrollment, they were treated with thrombopoietin receptor agonist (eltrombopag). Five patients responded positively, showing a median platelet count of 115,000 (39,000 to 433,000)/uL. The median dose of eltrombopag used was 1.3 (0.8 to 2.2) mg/kg/day. The quality of life (QoL) improved for all patients, with their median overall score using a Pediatric QoL questionnaire showing 25.0% improvement. Median scores also showed improvements in each sphere of life functioning as physical (30.8%), emotional (26.4%), social (16.4%), and school (21.4%). The present report demonstrated that a select group of cITP patients, with low platelet count and bleeding symptoms, benefitted from treatment with eltrombopag, as shown by increased platelet counts and improved QoL. Keywords: Chronic ITP, Thrombopoietin receptor agonist, Children

CP-080 Thrombopoietin receptor agonist treatment in idiopathic thrombocytopenic purpura

2015 ◽  
Vol 22 (Suppl 1) ◽  
pp. A32.1-A32
Author(s):  
MH García Lagunar ◽  
I Español Morales ◽  
M Martínez Penella ◽  
I Muñoz García ◽  
M Gutiérrez Cívicos ◽  
...  
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Receptor Agonist ◽  
Thrombocytopenic Purpura ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist

scholarly journals Thrombopoietin Receptor Agonist Eltrombopag Prevents Insulin Resistance and Synaptic Pathology via HIF1α/COX2/Sirt1 Signaling Pathway 

2021 ◽  
Author(s):  
he yu ◽  
xuebao wang ◽  
leping liu ◽  
baihui chen ◽  
shuya feng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Learning And Memory ◽  
Receptor Agonist ◽  
Synaptic Activity ◽  
Sirtuin 1 ◽  
High Dose ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Synaptic Formation

Abstract Background: Insulin resistance has been reported to be closely correlated with the pathogenesis of MHE. The mechanism underlying the effects of thrombopoietin receptor agonist eltrombopag (ELT) on synaptic activity and formation involved in MHE pathogenesis remains unclear. Methods: The effect of ELT on neurodegeneration and insulin resistance was examined in the primary rat neurons and an MHE rat model. Results: We found that the level of thrombopoietin receptor c-MPL (MPL) expression was decreased in MHE brains, and ELT administration improved insulin resistance, alleviated the destruction of synaptic formation and enhanced learning and memory in the MHE rats, indicating the relationship between dowregulated ELT and insulin resistance. Then in vitro, ELT treatment ameliorated the impairment of glucose uptake, indicating the reduction of insulin resistance. High dose of glucose inhibited insulin-stimulated downregulation of Hypoxia-inducible factor-1α (HIF1α) expression, the inhibition of inflammatory response and upregulation of sirtuin-1 (Sirt1), destruction of synaptic formation and activity, which were all reversed by ELT treatment in insulin resistant neurons.Conclusions: These results indicate that ELT is a promising potential therapeutic agent for insulin resistance and defect in learning and memory.

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