Gene therapy for homozygous β -thalassemia. Is it a reality? Journal Article


Authors: Boulad, F.; Riviere, I.; Sadelain, M.
Article Title: Gene therapy for homozygous β -thalassemia. Is it a reality?
Abstract: The β-thalassemias are genetic disorders that are caused by the absent or insufficient production of the β-chain of hemoglobin. This deficiency causes ineffective erythropoiesis and hemolytic anemia. Without treatment, the severe form of the disease is lethal within the first decade of life. The only curative therapeutic option to date is allogeneic bone marrow transplantation from a matched, related donor, which carries a low risk of morbidity and mortality. Most patients, however, lack a matched donor and are thus managed with palliative therapy, consisting of lifelong transfusion therapy combined with pharmacological chelation to curb iron accumulation. Despite a major improvement in the chelation therapy and supportive care, the major cause of death in these patients is cardiac failure due to secondary hemochromatosis. The goal of globin gene therapy is to offer a potentially curative treatment to patients lacking a matched, related donor, based on the transfer of a regulated β-globin gene in autologous CD34 hematopoietic cells collected following G-CSF mobilization. Our clinical trial at Memorial Sloan-Kettering Cancer Center builds on a 20-year long investigation to develop an erythroid-specific vector to regulate β-globin transgene expression in the progeny of transduced hematopoietic stem cells. To minimize the risks to the patient, the genetically modified cells will be infused after extensive biosafety testing of the transduced cells and following the administration of a reduced intensity (non-myeloablative) conditioning regimen. The protocol will be offered to patients with transfusion-dependent ß-thalassemia who are 15 years or older and lack a matched, related donor. © 2009 Informa UK, Ltd.
Keywords: adult; busulfan; clinical trial; fatigue; mortality; nonhuman; clinical trials as topic; conference paper; cd34 antigen; erythropoiesis; morbidity; palliative therapy; allogenic bone marrow transplantation; bone pain; stem cell transplantation; hematopoietic stem cell transplantation; gene transfer; genetic transduction; transduction, genetic; gene expression regulation; homozygosity; cause of death; donor; heart failure; gene therapy; lentivirus; thalassemia; globin; granulocyte colony stimulating factor receptor; hemoglobin beta chain; iron; lentivirus vector; retrovirus vector; beta thalassemia; blood transfusion; chelation therapy; erythroid cell; globin gene; graft versus host reaction; hematopoietic cell; hemochromatosis; hemolytic anemia; progeny; reduced intensity conditioning; stem cell gene therapy; stem cell mobilization; transgene; beta-globins; beta-thalassemia; clinical protocols; hematopoietic stem cells; homozygote; transplantation conditioning
Journal Title: Hemoglobin
Volume: 33
Issue: SUPPL. 1
ISSN: 0363-0269
Publisher: Informa Healthcare  
Date Published: 2009-01-01
Start Page: S188
End Page: S196
Language: English
DOI: 10.3109/03630260903351866
PUBMED: 20001625
PROVIDER: scopus
DOI/URL:
Notes: --- - "Export Date: 30 November 2010" - "CODEN: HEMOD" - "Source: Scopus"
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MSK Authors
  1. Farid Boulad
    255 Boulad
  2. Michel W J Sadelain
    462 Sadelain
  3. Isabelle C Riviere
    168 Riviere