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Study finds nonviral gene therapy for severe hemophilia a is safe with early signs of benefit

BOSTONA phase I study led by researchers at Beth Israel Deaconess Medical Center has demonstrated that a factor VIII gene therapy-based treatment for severe hemophilia A is safe and well-tolerated. The results of this first human investigation of hemophilia A gene therapy also showed that the treatment, which was derived from patients own cells, may be effective in reducing the occurrence of spontaneous bleeding, a frequent and potentially lethal symptom of the severe form of the disorder. The findings are published in the June 7 issue of the New England Journal of Medicine.

The study, which utilized a nonviral gene therapy system developed by Transkaryotic Therapies (TKT) of Cambridge, Mass., involved six patients with severe hemophilia A, a deficiency of the blood clotting protein called factor VIII. Each patient was treated with his own cells after the cells were genetically modified in a laboratory to express factor VIII. While the study was conducted to determine whether the treatment was safe, the researchers found that four of the six patients had elevated plasma levels of factor VIII activity after receiving the genetically modified cells. This increase coincided with a decrease in bleeding and/or a reduction in the amount of factor VIII needed to treat bleeding. In addition, two of these patients experienced no episodes of spontaneous bleeding during a 10 month period following treatment.

"It is greatly encouraging to see that this treatment is safe, that no immune responses to factor VIII developed in any patient, and that no patient developed side effects from the genetically modified cells," says David A. Roth, M.D., director of hemophilia clinical research at Beth Israel Deaconess and the studys principal investigator and lead author. "There is still a lot of work that needs to be done on these and other patients before we can move on to future studies to formally evaluate efficacy, but we are optimistic based on the clinical responses we ob
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Contact: Bill Schaller
bill_schaller@caregroup.harvard.edu
617-632-8062
Beth Israel Deaconess Medical Center
6-Jun-2001


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