What is the focus of investigational treatments for beta thalassemia?

Updated: May 07, 2021
  • Author: Pooja Advani, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Emerging therapies include pharmacologic agents that induce fetal hemoglobin, Jak2 inhibitors to reverse splenomegaly, hepcidin-related compounds to improve iron metabolism, and gene therapy aimed at delivering the beta globin gene into cells by a viral vector. [22]

Because fetal globin gene expression is associated with a milder phenotype, approaches to enhance intracellular Hb F levels (through drugs that activate gamma-globin gene expression) are under investigation. The two most widely studied drugs in this area are butyrates and hydroxyurea. [23] More recently, new therapeutic targets have been reported, such as BCL11A, which regulates fetal hemoglobin expression. [24, 25]

Other therapeutic approaches currently being investigated include the following [26, 27] :

  • Demethylating agents (eg, decitabine, 5-azacytidine)
  • Histone deacetylase (HDAC) inhibitors (eg, vorinostat, panobinostat)
  • Immunomodulating agents (eg, pomalidomide)
  • Short-chain fatty acid derivatives (eg, arginine butyrate, sodium phenylbutyrate)

Sotatercept (ACE-011) is a promising activin type IIA receptor fusion protein that has been recently reported to improve anemia in patients with non–transfusion-dependent thalassemia intermedia. [28]

Improvement in anemia has been reported with administration of erythropoietin in several studies; however, well-controlled clinical trials have not been performed. The postulated mechanism of action of erythropoietin is that increasing the erythroid mass (pathologic and less pathologic RBCs) and, thus hemoglobin, stimulates fetal hemoglobin, increases iron use, and reduces oxidative stress. [29]

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