論文 - 詳細
| RRC ID | 77345 |
|---|---|
| 著者 | Steinberg MH. |
| タイトル | Targeting fetal hemoglobin expression to treat β hemoglobinopathies. |
| ジャーナル | 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. |
| 巻・号 | 26(4) |
| ページ | 347-359 |
| 公開日 | 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 |
| リソース情報 | |
| ヒト・動物細胞 | HUDEP-2(RCB4557) |