Impact of Hemoglobin Biophysical Studies on Molecular Pathogenesis and Drug Therapy for Sickle Cell Disease

This article, by NIH Distinguished Investigator William A. Eaton, MD, PhD, Chief of the NIDDK’s Laboratory of Chemical Physics, dives deep into biophysical research to date exploring the molecular pathogenesis of sickle cell disease (SCD) and how it has informed various approaches to drug therapy targeting HbS polymerization. While the review focuses largely on traditionally used and newer anti-sickling agents, it also mentions other types of therapy, such as with the FDA- approved agents crizanlizumab, an antibody that binds P-selectin (a protein that adheres cells to the vascular endothelium) and “presumably acts by decreasing transit times and therefore the probability of sickling in the micro-vasculature”; and glutamine, which reduces oxidative stress, “one of the multiple sequelae of HbS polymerization.”

Molecular Aspects of Medicine