A chemically modified protein that may help in treating genetic bleeding disorder Hemophilia A has been discovered by researchers at the University of Texas Health Science Center at Houston.
With lack of blood-clotting protein Factor VIII (FVIII), people with Hemophilia A typically receive injections of FVIII derived from plasma or produced synthetically to control potentially life-threatening episodes of bleeding.
However, as many as 1 in 3 people with Hemophilia A produce inhibitor antibodies, which attack the externally administered FVIII and negate its blood-clotting benefits.
To fight this problem, senior author Sudhir Paul, Ph.D., at The University of Texas Medical School at Houston and colleagues developed a chemically modified version of FVIII, which during laboratory tests neutralized these inhibitor antibodies, thus paving the way for the correction of the blood-coagulating process.
The modification is called electrophilic FVIII analog (E-FVIII).
"It's a two-step process. The E-FVIII permanently inactivates the antibodies that inhibit blood clotting in 20 to 30 percent of patients receiving Factor VIII replacement therapy. Once the antibodies are cleared, additional FVIII can be injected," Paul said.
The study, led by Stephanie Planque, involved blood donated by eight people with FVIII-resistant Hemophilia A.
Co-author Keri Smith, Ph.D., an assistant professor of pathology and laboratory medicine at the UT Medical School at Houston, said that today, people with FVIII-resistant Hemophilia A have limited treatment options.
Those options include bypass therapy or multiple FVIII injections. Both are prohibitively expensive and often ineffective to meet emergency blood-clotting needs.
Smith said that E-FVIII might provide a more economically feasible method of treating inhibitor antibodies.
According to Paul, the next step involves clinical trials.
"E-FVIII is a first generation reagent. Future genetic and chemical manipulations may help develop improved E-FVIII analogs," Paul said.
The study appears in the May 2 issue of the Journal of Biological Chemistry.