Modified protein treats haemophilia in mice
Scientists have engineered a human clotting factor into a safe and effective treatment that cured haemophilia in mice. By changing the shape of the protein they made it safer and longer lasting than its natural counterpart meaning that it could be developed into a new treatment for a range of bleeding disorders.
Blood clotting is a complex process involving a cascade of proteins activating each other. This process eventually leads to a blood clot forming. Bleeding disorders are often caused by the absence or malfunction of one of the many proteins involved in the clot-forming pathway. This can lead to spontaneous bleeding and puts the patient at great risk of severe blood loss from even minor injuries. Haemophilia is one such disease and is caused by a genetic mutation that mostly affects males. Treatments for clotting-disorders include synthetic forms of natural clotting factors, but they are costly and can cause side-effects by triggering immune reactions.
FXa is one of the proteins involved in the clotting pathway. However, it cannot be used as a treatment to stimulate clotting because in its natural form it is broken down in the body very quickly.
Scientists modified the shape of FXa so that it is more stable in the blood and does not interact with the immune system. This means it will stay active for longer and avoid many of the side-effects of current treatments.
To test their custom-designed FXa the researchers injected it into mice that had been genetically engineered to carry the haemophilia mutation. These mice lost less blood than mice given a placebo or a medicine called FVIIa, a current treatment for the disease.
The researchers believe the custom FXa could be developed into a new medicine for clotting disorders and could also be used to induce blood clotting in other situations, such as in severe trauma victims.