Related Experiment Video
Updated: Aug 10, 2026

Characterization of Sickling During Controlled Automated Deoxygenation with Oxygen Gradient Ektacytometry
Published on: November 5, 2019
Pathophysiologically based drug treatment of sickle cell disease
1Center of Excellence in Sickle Cell Disease, E248, Boston Medical Center, 88 E. Newton Street, Boston, MA 02118, USA. mhsteinb@bu.edu
Abstract:
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.
Related Concept Videos
Pharmacogenomics: Identification of New Drug Targets
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
Principles of Drug Action
Drugs can be agonists or antagonists. Like the endogenous ligands, agonists always bind and activate the target to produce a cellular response. Agonist binding induces a conformational change which in turn...
Drug toxicity: Idiosyncratic Reactions
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
Cardiovascular Drugs: Classification based on Therapeutic Indications
