December 07, 2007
Sickle cell disease (SCD) is an inherited blood disorder caused by a genetic
mutation that leads to the generation of a mutant form of the beta-globin chain
of hemoglobin (Hb). Red blood cells containing Hb with this mutant beta-globin
chain change shape upon deoxygenation and this causes them to get stuck in blood
vessels, depriving the surrounding tissues of oxygen, which can lead to organ
damage. Although hydroxyurea, a treatment for SCD that works by increasing fetal
Hb (HbF) expression, benefits some adults with moderate and severe SCD, it does
not work for all individuals. Now, hope for a new therapy for SCD has been
provided by the work of Laure A. Moutouh-de Parseval and colleagues working for
Celgene Corporation.
In the study, lenalidomide and pomalidomide, immunomodulatory anticancer drugs,
were both shown to be more effective than hydroxyurea at inducing HbF expression
by erythrocytes derived in vitro from CD34+ cells from healthy individuals. In
addition, the effects of pomalidomide and hydroxyurea on HbF expression were
synergistic. As pomalidomide was able to induce HbF expression in CD34+ cells
from patients with SCD, the authors suggested that it might provide a new
therapy for SCD, either alone or in combination with hydroxurea. Furthermore,
because the induction of HbF has been shown to be of some benefit to individuals
with beta-thalassemia (a hereditary anemia caused by decreased beta-globin
production), the authors also suggested that pomalidomide might be a good
therapeutic for the treatment of beta-hemoglobinopathies other than SCD, such as
beta-thalassemia.
Journal of Clinical Investigation