ScienceDaily (Jan. 22, 2002) — MINNEAPOLIS / ST. PAUL -- University of Minnesota researchers have demonstrated that it may be possible to treat hemophilia A through the use of human blood outgrowth endothelial cells, or BOECs, as a vehicle for gene therapy. Lead researcher Robert Hebbel, M.D., the George Clark Professor and vice chair for research, department of medicine, reports that the use of BOECs has "resulted in sustained and therapeutic levels of factor 8 (FVIII) in mice and may comprise an effective therapeutic strategy for use in gene therapy for humans with hemophilia A." The results of this gene therapy, published in the January 15 issue of Blood, may pave the way for testing the therapy in humans.

Hemophilia A is an inherited blood disorder that affects one in 5,000 males and results in spontaneous bleeding due to the lack of coagulation factor 8 (FVIII) in the blood. Because hemophilia is such a severe disease, and because it is caused by absence of a replaceable blood protein, there has been a high level of interest in developing a gene therapy approach for its treatment. While there are currently some ongoing Phase I clinical studies of gene therapy for humans for hemophilia B (a related disorder that affects a different coagulation factor), development of gene therapy for hemophilia A has lagged behind. Current clinical therapy generally calls for the replacement of factor VIII after the patient has had some trouble.

The ex vivo process devised by Hebbel utilizes BOECs as carriers for gene therapy. The process begins with a blood sample taken from the patient as a source for autologous BOECs. (This use of autologous cells eliminates the concern for immunological compatibility or disease-tainted blood sources). The BOECs are separated from the blood and cultured in the lab and then transfected with a nonviral plasmid vector carrying the gene for human coagulation factor VIII. After allowing them to further expand, those stably transfected BOECs are then given back to the patient, where they seek out the bone marrow and the spleen and start to divide.

"The results we've seen in our mouse studies show long-term attainment of robust levels of factor VIII that would be therapeutic in a human," said Hebbel. "While we typically would call a five percent increase in FVIII level a good result, we've seen over a hundred percent of normal amounts of factor VIII in these mice. The results are very exciting and provide a strong rationale for proceeding to preclinical trials in dogs and clinical trials in humans."

The development of BOEC technology for gene therapy of hemophilia has been supported by the National Insitutes of Health and the Octagen Corp.

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