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Modified FVIII Protein May Block Inhibitors

Researchers from The University of Texas Health Science Center at Houston are developing a chemically modified protein that could eventually be used as a therapy for difficult-to-treat hemophilia A patients with inhibitors.

Approximately 15% to 30% of hemophilia A patients develop inhibitors, a challenging complication with limited and expensive treatment options. When the body’s immune system recognizes infused clotting factor as a foreign substance, it releases antibodies, called inhibitors, in response. The antibodies attack the factor, inhibiting its effects.

Senior author Sudhir Paul, PhD, at The University of Texas Medical School at Houston, lead author Stephanie Planque, a PhD candidate, and their colleagues collaborated with Kathleen P. Pratt, PhD, of the Puget Sound Blood Center and Division of Hematology at the University of Washington in Seattle. 

In laboratory tests, Paul’s team discovered that electrophilic factor VIII analog (E-FVIII), a modified protein, could neutralize inhibitor antibodies, thus clearing the way for follow-up infusions of factor VIII. 

“It’s a two-step process,” said Paul. “The E-FVIII permanently inactivates the antibodies that inhibit blood clotting in 20% to 30% of patients receiving factor VIII replacement therapy. Once the antibodies are cleared, additional FVIII can be injected.” The study used blood donated by eight people with FVIII-resistant hemophilia A. The next step for Paul and his colleagues is to conduct clinical trials involving E-FVIII.

 “Covalent inactivation of factor VIII antibodies from hemophilia A patients by an electrophilic FVIII analog,” was published in the May 2, 2008, issue of The Journal of Biological Chemistry.

This research was supported by grants from the Hemophilia Association of New York, Hemophilia of Georgia and the National Institutes of Health.

Source: ScienceDaily, May 21, 2008


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