Hemophilia B is an X-linked bleeding disorder resulting from a deficiency of coagulation factor IX. Studies of patients treated with prophylactic factor IX protein infusions to maintain plasma levels >1 % show that chronic arthropathy and life-threatening hemorrages may be prevented. This experience and ongoing concern about blood-born diseases transmitted through use of factor concentrates form the rationale for a gene transfer approach to this disease. Our group has developed solid preclinical experience with gene transfer using a adeno-associated viral (AAV) vector to mediate transfer of the gene for factor IX to muscle. We propose to carry out studies in humans with severe hemophilia B. The first study will be a dose-escalation study in which 3 groups of 3 patients will be evaluated for toxicity. The next study will be a dose finding and efficacy study to determine the dose of AAV-hFIX that results in plasma levels of factor IX of 5-7% and to demonstrate the efficacy of this dose in a group of approximately 25 patients by assessing number of bleeds, factor concentrate use, and clinical effect using a hemophilia-specific health assessment tool. We will also characterize the human immune response to vector proteins and the expressed factor IX transgene. Finally, we will assess the transmission of vector sequences to body fluids. Enrollment of the first five patients is now complete.
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