Von Willebrand Factor (VWF) is a large multimeric plasma glycoprotein that performs two essential roles in haemostasis. Firstly, VWF mediates platelet adhesion to sites of vessel injury under high shear stress and secondly, VWF is the carrier molecule of coagulation factor VIII (FVIII), prolonging its otherwise short halflife.
Deficiency of VWF results in the bleeding disorder von Willebrand disease (VWD), which is the most common inherited bleeding disorder, affecting ~3-4 individuals in every 100,000 representing 1.3% of the population. Treatment of VWD is usually performed with either desmopressin to promote release of VWF or with replacement therapy involving the administration of VWF concentrates, at a cost to the NHS of approximately £10 million per year in drug alone.
The present invention provides a gene therapy or recombinant protein approach for the treatment of VWD or haemophilia. A team at Imperial College London have produced a novel truncated VWF variant in which several domains are deleted, yet sharing the function of the full-length protein. In particular it demonstrates normal multimer formation, is able to interact with collagen under static conditions and the ability of the variant to capture platelets under shear stress is not altered. The variant can therefore be used in place of the full-length protein in the treatment of VWD or haemophilia.
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