Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amgen Inc is developing AMG-531, a peptibody that binds to the thrombopoietin receptor Mpl, for the potential treatment of immune thrombocytopenic purpura (ITP), chemotherapy-induced thrombocytopenia (CIT) and thrombocytopenia in myelodysplastic syndrome (MDS). Results of the US phase III trial in ITP are expected to be available in the second half of 2006, while a phase II trial in CIT is still underway. A Japanese phase II ITP study has been initiated, as has a phase II trial of MDS patients in the US and France.
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PMID:Drug evaluation: AMG-531 for the treatment of thrombocytopenias. 1700 62

Supportive care constitutes the basis of the management of patients with myelodysplastic syndromes (MDS). Appropriate treatment of cytopenia, as well as of other related complications, not only improves quality of life but also may positively affect the overall survival of patients. Anemia is the most common cytopenia in MDS, and the requirement for regular transfusions is a major clinical problem for patients with low-risk MDS. An important therapeutic goal in this patient group is to maintain acceptable hemoglobin levels without transfusions. Today, this goal can be achieved by treatment with erythropoietin (Epo) +/- granulocyte colony-stimulating factor (G-CSF), or by more targeted treatment such as antithymocyte globulin or lenalidomide in around 50% of patients. For the remaining patients, and for those who lose their therapeutic response, chronic transfusion therapy, with or without the addition of chelating agents, is the only option and it is important that this treatment is scheduled to meet the needs of the individual patient. Severe thrombocytopenia has recently been reported to respond to thrombopoietic agents, such as AMG 531.
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PMID:Supportive care and use of hematopoietic growth factors in myelodysplastic syndromes. 1817 65

Thrombocytopenia can be seen in a variety of disease states, including immune mediated thrombocytopenic purpura (ITP) and myelodysplastic syndromes (MDS). The most concerning complication is the development of hemorrhagic complications that may contribute to patient morbidity and mortality. The ligand thrombopoeitin (TPO) and its interaction with its receptor (c-mpl) are important in platelet production. Thrombopoietic agonists can help in the management of thrombocytopenia related to these conditions. Amgen Megakaryopoiesis Protein 531 (AMG-531) (Romiplostim) is a recombinant TPO with a peptide fragment that shares no sequence homology with endogenous TPO, preventing the production of neutralizing antibodies. Recent studies have shown that it is effective in raising platelet counts, and is well tolerated in ITP and MDS patients. In this review, we discuss thrombopoiesis regulation by TPO; the chemistry, pharmacokinetics and pharmacodynamics of AMG-531 in animals and humans; the pathophysiological mechanisms leading to thrombocytopenia in ITP and MDS; and clinical trials demonstrating its efficacy in treating thrombocytopenia.
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PMID:The role of AMG-531 in the treatment of thrombocytopenia in idiopathic thrombocytopenic purpura and myelodysplastic syndromes. 1854 31

Platelets play a pivotal role in maintaining hemostatic competence. Thrombocytopenia, irrespective of its etiology, is associated with a risk for bleeding. Treatment modalities for chronic idiopathic thrombocytopenic purpura (ITP) are numerous, but the response is variable, often disappointing and associated with high risks. Better understanding of the pathophysiology of chronic ITP, indicating impaired platelet production rather than simply increased turnover, led to clinical trials aimed at increasing platelet production with thrombopoietin receptor agonists. To date, two compounds have been investigated extensively, romiplostim (AMG-531, Nplate) and eltrombopag (SB-497115, Promacta, Revolade). The success of this treatment further paved the way for evaluating its efficacy in raising platelet counts in hepatitis C virus (HCV)-related infection and myelodysplastic syndrome. Although there is less experience in hepatitis C than in chronic ITP, preliminary data are highly promising. This review will focus on the experience gained with eltrombopag in chronic ITP and HCV-related thrombocytopenia.
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PMID:Eltrombopag in chronic idiopathic thrombocytopenic purpura and HCV-related thrombocytopenia. 1934 29

The myelodysplastic syndromes (MDS) represent a group of clonal disorders that result in ineffective hematopoiesis and are associated with an increased risk of transformation into acute leukemia. MDS arises from hematopoietic stem cells (HSCs); therefore, successful elimination of MDS HSCs is an important part of any curative therapy. However, current treatment options, including allogeneic hematopoietic cell transplantation (HCT), often fail to ablate disease-initiating MDS HSCs, and thus have low curative potential and high relapse rates. Here, we demonstrate that human HSCs can be targeted and eliminated by monoclonal antibodies (mAbs) that bind cell-surface CD117 (c-Kit). We show that an anti-human CD117 mAb, SR-1, inhibits normal cord blood and bone marrow HSCs in vitro. Furthermore, SR-1 and clinical-grade humanized anti-human CD117 mAb, AMG 191, deplete normal and MDS HSCs in vivo in xenograft mouse models. Anti-CD117 mAbs also facilitate the engraftment of normal donor human HSCs in MDS xenograft mouse models, restoring normal human hematopoiesis and eradicating aggressive pathologic MDS cells. This study is the first to demonstrate that anti-human CD117 mAbs have potential as novel therapeutics to eradicate MDS HSCs and augment the curative effect of allogeneic HCT for this disease. Moreover, we establish the foundation for use of these antibody agents not only in the treatment of MDS but also for the multitude of other HSC-driven blood and immune disorders for which transplant can be disease-altering.
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PMID:Anti-CD117 antibody depletes normal and myelodysplastic syndrome human hematopoietic stem cells in xenografted mice. 3107 63