Gene Therapy for Beta-Thalassemia Successful in Preclinical Trial

Results obtained in a preclinical trial have shown that human cells from patients with beta-thalassemia are susceptible to transfection and cure by a viral vector carrying the gene for beta-globin.

Individuals with mutations to the beta-globin gene are unable to manufacture sufficient amounts of hemoglobin. The anemia caused by this condition is characterized at the cellular level by apoptosis of cells in the bone marrow and inadequate production of blood cells. The condition is most commonly found in Mediterranean, Middle Eastern, and Asian populations.

As current treatment options are limited, investigators at the San Raffaele Telethon Institute for Gene Therapy (Milan, Italy) explored the possibility of treating beta-thalassemia by gene therapy. To this end, they created a lentiviral vector (GLOBE) that expressed a transcriptionally regulated human beta-globin gene. The GLOBE vector was used to transfect the beta-globin gene into cell cultures taken from beta-thalassemia patients.

Results published in the July 2010 online edition of the journal EMBO Molecular Medicine revealed that the procedure achieved a high frequency of transduction, restoration of hemoglobin synthesis, rescue from apoptosis, and correction of ineffective erythropoiesis. The procedure did not significantly affect the differentiating potential and the relative proportion of hematopoietic progenitors.

"Successful gene therapies are the results of very long studies and our research represents the most comprehensive preclinical analysis ever performed on cells derived from thalassemic patients,” said senior author Dr. Giuliana Ferrari, a senior researcher at the San Raffaele Telethon Institute for Gene Therapy. "We believe this study paves the way forward for the clinical use of stem cells genetically corrected using the GLOBE vector.”

"Currently treatments are limited to lifelong regular blood transfusions and iron chelation to prevent fatal iron overload. The alternative is bone marrow transplantation, an option open to less than 25% of patients,” said Dr Giuliana. "Our research has focused on gene therapy: by transplanting genetically corrected stem cells we can restore hemoglobin production and overcome the disorder. Diseases of the blood are good targets for gene therapy because it is possible to harvest stem cells from the patient's bone marrow.”

Related Links:
San Raffaele Telethon Institute for Gene Therapy