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Editorials
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Figure 1. Role of hepcidin and novel thiazolidinone compounds in the treatment of hemochromatosis and β-thalassemia. (A) Relationship between disease, genet- ic mutations, hepcidin levels, drug administration and phenotype in primary and secondary forms of hemochromatosis. (B) Potential mechanisms of action and ther- apeutic effects of new thiazolidinone compounds in hemochromatosis and β-thalassemia.
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ia-related molecules that converge on suppressing hep- cidin synthesis or increasing ferroportin expression (Figure 1A).2,3,13
Conversely, mutations in the TMPRSS6 gene lead to overexpression of hepcidin. In this case, patients suffer from a condition indicated as iron-refractory iron defi- ciency anemia or IRIDA.14 These individuals suffer from a form of anemia that typically does not improve with oral iron treatment, but requires parenteral iron administra- tion.14
The elucidation of these pathways and their associa- tion with disease led to the development of pharmacolog- ical compounds that increase hepcidin expression, mimic its activity, or decrease ferroportin activity, which can decrease iron absorption and improve iron overload in
primary and secondary forms of hemochromatosis (Figure 1A).15,16 Intriguingly, the same drugs also showed beneficial effects on anemia in animal models of non- transfusion-dependent thalassemia (Figure 1A).13,17,18 In this case, it was observed that these drugs not only decreased iron absorption, but also erythroid iron intake.13,17,18 In thalassemic erythroid progenitor cells, this can reduce the detrimental effects of oxidative stress trig- gered by the excess of iron and heme not included in nor- mal hemoglobin molecules.13,17,18 This improves the quali- ty and lifespan of red blood cells, and increases hemoglo- bin levels.13,17,18 The overall effect is to improve ineffective erythropoiesis and the associated iron overload (Figure 1A).
So far, most of the compounds identified as leading to
haematologica | 2019; 104(9)