Perspectives for the therapy of anemia of chronic diseases

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.