The genomics of new drugs in sickle cell disease.
The quality of life of patients with sickle cell disease in developed countries has improved significantly over the past two decades. Currently available measures to prevent the painful crises and the complications of the disease include the use of penicillin prophylaxis, antipneumonococcal vaccine, folate administration, chronic red cell transfusions in patients with cerebrovascular disease, iron chelating agents, fetal hemoglobin-enhancing agents, such as hydroxyurea, decitabine and butyrate, drugs that augment the endogenous nitric oxide levels and agents that restore red cell dehydration. Sickle cell patients show a broad phenotypic expression and a great variability in treatment response. Genetic association studies, which attempt to link polymorphisms with certain disease phenotypes and drug response, are taking the first steps in aiding individualized therapy in sickle cell patients in order to enhance efficacy and reduce toxicity.
Makis
Alexandros C
AC
Department of Paediatrics, University Hospital of Ioannina, Ioannina, Greece. alexandros.makis@medai.gr
Hatzimichael
Eleftheria C
EC
Stebbing
Justin
J
D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D000986:Antisickling Agents / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D002087:Butyrates / Q000627:therapeutic use; D000077209:Decitabine; D004351:Drug Resistance; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D009569:Nitric Oxide / Q000627:therapeutic use; D010597:Pharmacogenetics; D010641:Phenotype; D020442:Poloxamer / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D012460:Sulfasalazine / Q000627:therapeutic use; D043922:Toxicogenetics
D000986:Antisickling Agents; D002087:Butyrates; D020442:Poloxamer; D009569:Nitric Oxide; D012460:Sulfasalazine; D000077209:Decitabine; D001374:Azacitidine; D006918:Hydroxyurea