RRC ID 77345
Author Steinberg MH.
Title Targeting fetal hemoglobin expression to treat β hemoglobinopathies.
Journal Expert Opin Ther Targets
Abstract INTRODUCTION:Sickle cell disease and β thalassemia are the principal β hemoglobinopathies. The complex pathophysiology of sickle cell disease is initiated by sickle hemoglobin polymerization. In β thalassemia, insufficient β-globin synthesis results in excessive free α globin, ineffective erythropoiesis, and severe anemia. Fetal hemoglobin (HbF) prevents sickle hemoglobin polymerization; in β thalassemia HbF compensates for the deficit of normal hemoglobin. When HbF constitutes about a third of total cell hemoglobin, the complications of sickle cell disease are nearly totally prevented. Similarly, sufficient HbF in β thalassemia diminishes or prevents ineffective erythropoiesis and hemolysis.
AREAS COVERED:This article examines the pathophysiology of β hemoglobinopathies, the physiology of HbF, intracellular distribution, and the regulation of HbF expression. Inducing high levels of HbF by targeting its regulatory pathways pharmacologically or with cell-based therapeutics provides major clinical benefit and perhaps a 'cure.'
EXPERT OPINION:Erythrocytes must contain about 10 pg of HbF to 'cure' sickle cell disease. If HbF is the only hemoglobin present, much higher levels are needed to 'cure' β thalassemia. These levels of HbF can be obtained by different iterations of gene therapy. Small molecule drugs that can achieve even modest pancellular HbF concentrations are a major unmet need.
Volume 26(4)
Pages 347-359
Published 2022-4-1
DOI 10.1080/14728222.2022.2066519
PMID 35418266
MeSH Anemia, Sickle Cell* / drug therapy Carrier Proteins / genetics Fetal Hemoglobin / genetics Fetal Hemoglobin / metabolism Hemoglobin, Sickle / metabolism Hemoglobin, Sickle / therapeutic use Hemoglobinopathies* / therapy Hemoglobins / metabolism Hemoglobins / therapeutic use Humans beta-Thalassemia* / drug therapy beta-Thalassemia* / genetics
IF 5.473
Human and Animal Cells HUDEP-2(RCB4557)