Sickle cell anemia: targeting the role of fetal hemoglobin in therapy.
Sickle cell anemia results from the single amino acid substitution of valine for glutamic acid in the beta-chain owing to a nucleotide defect that causes the production of abnormal beta-chains in hemoglobin S. Abnormal hemoglobin chains form polymers in the deoxygenated state, leading to the characteristic sickle cells. The polymerization of deoxygenated hemoglobin S accounts for the pathologic changes in sickle cell disease. The main-stay of therapy in sickle cell disease aims to reduce the amount of sickled hemoglobin present through the prevention of polymerization and reversal of this process. One way of discouraging polymerization is to increase the level of fetal hemoglobin, which because of its high oxygen affinity, does not participate in the polymerization process. Fetal hemoglobin production may be induced pharmacologically or by the use of gene therapy and genetic engineering techniques.
Coleman
Emma
E
St Thomas Hospital, London, United Kingdom.
Inusa
Baba
B
D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D020868:Gene Silencing; D015316:Genetic Therapy; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D016372:RNA, Antisense / Q000627:therapeutic use
D016372:RNA, Antisense; D005319:Fetal Hemoglobin; D006918:Hydroxyurea