Sickle Cell Anemia Research Today is a free monthly online journal that collates and summarizes the latest research about Sickle Cell Anemia, including details on genetics, causes, symptoms.

Pathophysiologically based drug treatment of sickle cell disease.

Steinberg MH

Center of Excellence in Sickle Cell Disease, E248, Boston Medical Center, 88 E. Newton Street, Boston, MA 02118, USA. mhsteinb@bu.edu

Sickle cell disease is a systemic disorder that is caused by a mutation (Glu6Val) in the gene that encodes beta globin. The sickle hemoglobin molecule (HbS) is a tetramer of two alpha-globin chains and two sickle beta-globin chains, and has the tendency to polymerize when deoxygenated. HbS facilitates abnormal interactions between the sickle erythrocyte and leukocytes and endothelial cells, which trigger a complex pathobiology. This multifaceted pathophysiology provides the opportunity to interrupt the disease at multiple sites, including polymerization of HbS, erythrocyte density and cell-cell interactions. For example, it is possible to induce higher concentrations of fetal hemoglobin, which disrupts the pathology-initiating step of HbS polymerization. Furthermore, it is possible to improve the hydration of sickle erythrocytes and it might be feasible to counteract the endothelial, inflammatory and oxidative abnormalities of sickle cell disease. A therapeutic approach that targets several sites of pathobiology might be most promising.

Published 17 April 2006 in Trends Pharmacol Sci, 27(4): 204-10.
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