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.

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 Novel therapeutic choices in immune aplastic anemia

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1118
Author(s):  
Phillip Scheinberg
Keyword(s):  
Aplastic Anemia ◽  
Receptor Agonist ◽  
Single Agent ◽  
Severe Form ◽  
Hematopoietic Stem ◽  
Hematologic Response ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Upfront Therapy

Aplastic anemia (AA) in its severe form has historically been associated with high mortality. With limited supportive care and no effective strategy to reverse marrow failure, most patients diagnosed with severe AA (SAA) died of pancytopenia complications. Since the 1970s, hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have changed SAA's natural history by improving marrow function and pancytopenia. Standard IST with horse anti-thymocyte globulin plus cyclosporine produces a hematologic response rate of 60 to 70%. In the long term, about one-third of patients relapse, and 10 to 15% can develop cytogenetic abnormalities. Outcomes with either HSCT or IST are similar, and choosing between these modalities relies on age, availability of a histocompatible donor, comorbidities, and patient preference. The introduction of eltrombopag, a thrombopoietin receptor agonist, improved SAA outcomes as both salvage (second-line) and upfront therapy combined with IST. As a single agent, eltrombopag in doses up to 150 mg daily improved cytopenias in 40 to 50% in those who failed initial IST, which associated with higher marrow cellularity, suggesting a pan-stimulatory marrow effect. When eltrombopag was combined with IST as upfront therapy, overall (about 90%) and complete responses (about 50%) were higher than observed extensively with IST alone of 65% and 10%, respectively. Not surprisingly, given the strong correlation between hematologic response rates and survival in SAA, most (>90%) were alive after a median follow-up of 18 months. Longer follow-up and real-word data continue to confirm the activity of this agent in AA. The use of eltrombopag in different combinations and doses are currently being explored. The activity of another thrombopoietin receptor agonist in AA, romiplostim, suggests a class effect. In the coming years, the mechanisms of their activity and the most optimal regimen are likely to be elucidated.

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
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