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Perspectives for the therapy of anemia of chronic diseases
Affiliations- Department of Pharmacology and Toxicology, Collegium Medicum, University of Zielona Góra, Zielona Góra, Poland
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Abstract
The incidence of anemia of chronic disease (ACD) is underestimated, increases with age, and affects about 30% of the elderly. ACD treatment is currently based on the pharmacotherapy of diseases that caused anemia, erythropoiesis-stimulating agents, and parenteral administration of iron supplementation in case of iron deficiency. Increasing knowledge on the pathophysiology of ACD has resulted in the burst of research on the development of new drugs that are focused on three main areas. The first group of drugs includes substances that inhibit hepcidin transcription, namely direct and indirect bone morphogenetic protein 6 (BMP6) inhibitors and/or SMAD signaling pathway inhibitors, and drugs that regulate hepcidin transcription through STAT3 signaling pathway. The second group of drugs includes direct hepcidin inhibitors (e.g., aptamers, anticalin proteins, monoclonal antibodies) or substances that inhibit the binding of hepcidin to ferroportin. The third group of drugs improves erythropoiesis mainly by upregulation of erythropoietin and/or inhibition of proinflammatory cytokines. In the latter group, hypoxia-inducing factor stabilizers and IL-6 or TNFα antagonists are particularly important. This article discusses new drug groups and substances that are in different phases of development, including both preclinical and clinical studies, and focuses on the prospects of their use in ACD.
Abstract
The incidence of anemia of chronic disease (ACD) is underestimated, increases with age, and affects about 30% of the elderly. ACD treatment is currently based on the pharmacotherapy of diseases that caused anemia, erythropoiesis-stimulating agents, and parenteral administration of iron supplementation in case of iron deficiency. Increasing knowledge on the pathophysiology of ACD has resulted in the burst of research on the development of new drugs that are focused on three main areas. The first group of drugs includes substances that inhibit hepcidin transcription, namely direct and indirect bone morphogenetic protein 6 (BMP6) inhibitors and/or SMAD signaling pathway inhibitors, and drugs that regulate hepcidin transcription through STAT3 signaling pathway. The second group of drugs includes direct hepcidin inhibitors (e.g., aptamers, anticalin proteins, monoclonal antibodies) or substances that inhibit the binding of hepcidin to ferroportin. The third group of drugs improves erythropoiesis mainly by upregulation of erythropoietin and/or inhibition of proinflammatory cytokines. In the latter group, hypoxia-inducing factor stabilizers and IL-6 or TNFα antagonists are particularly important. This article discusses new drug groups and substances that are in different phases of development, including both preclinical and clinical studies, and focuses on the prospects of their use in ACD.
Keywords
anemia of chronic disease; hepcidin; cytokine; hypoxia-inducible factor; treatment
About this articleTitle
Perspectives for the therapy of anemia of chronic diseases
Journal
Issue
Pages
125-132
Published online
2020-09-01
Page views
161
Article views/downloads
224
DOI
10.2478/ahp-2020-0024
Bibliographic record
Acta Haematol Pol 2020;51(3):125-132.
Keywords
anemia of chronic disease
hepcidin
cytokine
hypoxia-inducible factor
treatment
Authors
Sylwia Sulimiera Michalak