Blood-clotting protein modified for people with hard-to-treat hemophiliaMay 20, 2008Pathologists at The University of Texas Health Science Center at Houston have developed a chemically modified protein that may help people with a hard-to-treat form of a genetic bleeding disorder known as Hemophilia A. The discovery and the results of pre-clinical tests appear in the May 2 issue of the Journal of Biological Chemistry. With a shortage of the 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. Unfortunately 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 combat this problem, scientists in the laboratory of Sudhir Paul, Ph.D., at The University of Texas Medical School at Houston, 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,'' said Paul, the senior author. "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." The study involved blood donated by eight people with FVIII-resistant Hemophilia A. Today, people with FVIII-resistant Hemophilia A have limited treatment options, said co-author Keri Smith, Ph.D., an assistant professor of pathology and laboratory medicine at the UT Medical School at Houston. Those options include bypass therapy or multiple FVIII injections. Both are prohibitively expensive and often ineffective to meet emergency blood-clotting needs. E-FVIII might provide a more economically feasible method of treating inhibitor antibodies, Smith said. There is no cure for Hemophilia A, and it primarily affects males. About one of every 7,000 males born in the United States has this condition. A person with hemophilia bleeds longer than a person without hemophilia. Stephanie Planque, who is lead author and is working towards her Ph.D. degree, helped conceive the chemical inactivation principle behind the study. The modified FVIII analog was produced by pathology faculty Hiroaki Taguchi, Ph.D., and Yasuhiro Nishiyama, Ph.D., using newly developed synthesis methods. Miguel Escobar, M.D., of the department of pediatrics and internal medicine at the UT Medical School at Houston and the Gulf States Hemophilia and Thrombophilia Center, led the clinical aspects of the work, and Kathleen Pratt, Ph.D., at the Puget Sound Blood Center and Division of Hematology, University of Washington, Seattle, contributed a genetically-produced protein that helped the study reach its conclusions. 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 wrote in the paper. University of Texas Health Science Center at Houston | |||||||||||||||||||||
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Related Hemophilia Current Events and Hemophilia News Articles UF researchers develop improved gene therapy agent Replacing one amino acid on the surface of a virus that shepherds corrective genes into cells could be the breakthrough scientists have needed to make gene therapy a more viable option for treating genetic diseases such as hemophilia, University of Florida researchers say. Skin flaps deliver cancer-fighting therapy, ASPS study reveals Using gene therapy, plastic surgeons have delivered cancer fighting proteins through skin flaps placed on cancerous tumors on rats with a 79 percent reduction in tumor volume. New stem cell technique improves genetic alteration UC Irvine researchers have discovered a dramatically improved method for genetically manipulating human embryonic stem cells, making it easier for scientists to study and potentially treat thousands of disorders ranging from Huntington's disease to muscular dystrophy and diabetes. NHLBI Issues First U.S. von Willebrand Disease Clinical Practice Guidelines The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, today issued the first clinical guidelines in the United States for the diagnosis and management of von Willebrand Disease (VWD), the most common inherited bleeding disorder. First demonstration of muscle restoration in an animal model of Duchenne muscular dystrophy Using a new type of drug that targets a specific genetic defect, researchers at the University of Pennsylvania School of Medicine, along with colleagues at PTC Therapeutics Inc. and the University of Massachusetts Medical School, have for the first time demonstrated restoration of muscle function in a mouse model of Duchenne's muscular dystrophy (DMD). Fragile X, Down syndromes linked to faulty brain communication The two most prevalent forms of genetic mental retardation, Fragile X and Down syndromes, may share a common cause, according to researchers at Stanford University School of Medicine. Fruit fly gene research may shed light on human disease processes Those small fruit flies buzzing around your bananas are more than pests—they may be allies in a fruitful search for clues to human diseases caused when genes malfunction. A transplant in time In hemophilia, a mutated gene prevents the production of a critical blood-clotting protein. Treatments for hemophilia and other such genetic diseases, when they exist, may consist of risky blood transfusions or expensive enzyme replacement therapy. Jumping gene could provide non-viral alternative for gene therapy A jumping gene first identified in a cabbage-eating moth may one day provide a safer, target-specific alternative to viruses for gene therapy. Rodent's bizarre traits deepen mystery of genetics, evolution A shadowy rodent has potential to shed light on human genetics and the mysteries of evolution. More Hemophilia Current Events and Hemophilia News Articles |
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