β-thalassemia is the most intensely studied genetic disorder that continues to
pose a significant public health challenge in spite of the innumerable and potentially
effective treatment options. Specifically, homozygous deletion or subfunctional mutation of
the gene contributing the β chains of the adult hemoglobin results in a clinical form referred
to as β-thalassemia major. This form of β-thalassemia is hard to treat. The treatment of β-
thalassemia major is currently based on the following main principles: a) regular blood
transfusion with treatment aimed at reducing tissue deposition of iron; b) modulation of the
fetal hemoglobin (HbF) switch to restart the production of HbF; c) allogeneic
hematopoietic stem cell transplantation; and d) approaches aimed at preventing or treating
the common complications of β-thalassemia major like infections, cardiac and hepatic
dysfunction and osteoporosis. The past decade has witnessed path-breaking advances with
regard to all of these therapeutic alternatives. For example, iron chelators like
desferrioxamine, deferasirox and deferiprone have led to an increased patient compliance
and decreased rates of iron deposition; more accurate diagnostic methods based on the
magnetic resonance imaging have helped to better define and plan management of iron
overload; several classes of HbF inducers have been identified and exciting opportunities
are being recognized based on a combination of these inducers; a plethora of agents are
available for the prevention and treatment of common complications; and, most
significantly, phenomenal advances have been made in the direction of gene therapy of β-
thalassemia major. In this chapter, we present a compiled account of the recent advances on
these fronts and also conjecture on the possible future directions these achievements are
likely to take.
Keywords: β-thalassemia major, treatment, iron overload, iron chelation,
splenectomy, osteoporosis, bone marrow transplantation, hematopoietic stem
cells, gene therapy, lentivirus.
