Researchers at the Medical College of Wisconsin, Milwaukee, have developed a new approach to treating the bleeding disorder haemophilia, which also promises to get around one of the most common problems associated with the disease. Haemophilia occurs when a patient inherits a defective copy of a gene coding for Factor VIII, a lynchpin in the blood's coagulation pathway. The gene is bourne on the X chromosome, which explains why men, who only have one X chromosome, are more commonly affected than women. Haemophilia can be controlled by regular replacement injections of Factor VIII, but in up to 30% of patients the body begins to produce antibodies, called inhibitors, against the therapeutic Factor VIII, preventing it from working. Under these circumstances doctors are forced to resort to extremely costly drugs which can push the price of treating a single patient beyond US$1 million. To get around the problem Robert Montgomery and his colleagues have produced the cellular equivalent of a Trojan horse. Using engineered haemophiliac mice, the researchers added a healthy copy of the Factor VIII gene to the stem cells in the mouse bone marrow which make platelets - tiny pieces of cells which help to plug holes in blood vessels. The Factor VIII remained hidden inside the platelet, away from the immune system, until an injury occurred. At this point, platelets at the site of the injury then discharged their cargo of Factor VIII where it helped to orchestrate blood clotting. To simulate a patient with antibodies against Factor VIII the researchers then injected the mice with 5,000-10,000 times as much antibody as would be seen in a patient - and the approach still worked. This suggests that if a patient's bone marrow stem cells are collected, a healthy copy of the Factor VIII gene added using a virus, and then the platelet-forming cells are returned to the patient, it might be possible to effect a cure.
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