Prenatal Gene Therapy Corrects Hemophilia B In Mice

NEW YORK (Reuters Health) - Introduction of human factor IX protein with prenatal gene therapy can correct hemophilia B in mice, according to a report in the November issue of Blood. In another study, researchers describe the creation of new murine hemophilia B models that more closely mimic the human disease.

Dr. Simon N. Waddington, from Imperial College London, and colleagues note that although recombinant protein substitution is an effective treatment for hemophilia B, it is expensive and inhibitory antibodies may develop. Therefore, there is a need for a treatment that can permanently correct the disease without inducing immune reactions.

To address this goal, the researchers created a HIV-based lentiviral vector containing human factor IX protein. This construct was then injected into the fetal circulation of immunocompetent mice with and without hemophilia B.

Treatment with the gene therapy provided a long-term increase in plasma factor IX levels. In addition, the animals displayed a marked improvement in blood coagulability and all stopped bleeding rapidly after venipuncture.

The gene therapy also appeared to be safe and there was no evidence of humoral or cellular immunity against the protein, liver dysfunction, or vector spread outside of the fetal circulation.

"These data constitute a very useful step toward application of fetal gene therapy for prevention of hemophilia," say the authors.

In the second study, Dr. Katherine A. High, of The Children's Hospital of Philadelphia, and colleagues set out to generate a murine model of hemophilia B that did not rely on gene deletions, a relatively rare etiology in humans. Instead, the researchers created several models that involved mutations in the factor IX gene.

"These new mouse models faithfully mimic the mutations causing human disease, and will prove useful for testing novel therapies for hemophilia," the investigators conclude.

Source: Blood 2004;104:2714-2721,2767-2774. [ Google search on this article ]

MeSH Headings: Animal Diseases : Biological Therapy : Disease Models, Animal : Genetic Engineering : Genetic Techniques : Investigative Techniques : Therapeutics : Gene Therapy : Analytical, Diagnostic and Therapeutic Techniques and Equipment : Diseases