An Expert Overview on Therapies in Non-Transfusion-Dependent Thalassemia: Classical to Cutting Edge in Treatment

Abstract

The thalassemia issue is a growing worldwide health concern that anticipates the number of patients suffering from the disease will soon increase significantly. Patients with β-thalassemia intermedia (β-TI) manifest mild to intermediate levels of anemia, which is a reason for it to be clinically located between thalassemia minor and β-thalassemia major (β-TM). Notably, the determination of the actual rate of β-TI is more complicated than β-TM. The leading cause of this illness could be partial repression of β-globin protein production; accordingly, the rate of β-globin gene repression is different in patients, and the gene repression intensity creates a different clinical status. This review article provides an overview of functional mechanisms, advantages, and disadvantages of the classic to latest new treatments for this group of patients, depending on the disease severity divided into the typical management strategies for patients with β-TI such as fetal hemoglobin (Hb) induction, splenectomy, bone marrow transplantation (BMT), transfusion therapy, and herbal and chemical iron chelators. Recently, novel erythropoiesis-stimulating agents have been added. Novel strategies are subclassified into molecular and cellular interventions. Genome editing is one of the efficient molecular therapies for improving hemoglobinopathies, especially β-TI. It encompasses high-fidelity DNA repair (HDR), base and prime editing, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 procedure, nuclease-free strategies, and epigenetic modulation. In cellular interventions, we mentioned the approach pattern to improve erythropoiesis impairments in translational models and patients with β-TI that involve activin II receptor traps, Janus-associated kinase 2 (JAK2) inhibitors, and iron metabolism regulation.

Keywords:

• β-Thalassemia intermedia (β-TI)
• novel pharmacological drugs
• gene editing
• clustered regularly interspaced short palindromic repeats (CRISPR)/cas9

Acknowledgements

The authors acknowledge all the individuals who contributed to this research at Shiraz University of Medical Sciences, Shiraz, Iran. The authors would also like to thank Mrs. Sheryl Nikpoor (editor of the Iranian Journal of Science and Technology, Transactions A: Science; [email protected]) for English editing.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

All authors declared that no financial support was received from any organization for the submitted article.