Author:

Keywords:

Deamino Arginine Vasopressin, Gene Therapy, Humans, Interleukin-11, von Willebrand Disease, von Willebrand Factor, Science & Technology, Life Sciences & Biomedicine, Hematology, PLATELET GLYCOPROTEIN IB, RECOMBINANT HUMAN INTERLEUKIN-11, SEVERE VONWILLEBRAND DISEASE, FACTOR-CLEAVING PROTEASE, HUMAN ENDOTHELIAL-CELLS, FACTOR-DEFICIENT MICE, FACTOR-VIII, GENE-THERAPY, HEMOPHILIA-A, DESMOPRESSIN DDAVP, Genetic Therapy, von Willebrand Diseases, 1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine, Immunology, 3101 Biochemistry and cell biology, 3201 Cardiovascular medicine and haematology, 3213 Paediatrics

Abstract:

von Willebrand factor (VWF) is a large multimeric adhesive glycoprotein with complex roles in thrombosis and hemostasis. Abnormalities in VWF give rise to a variety of bleeding complications, known as von Willebrand disease (VWD), the most common inherited bleeding disorder in humans. Current treatment of VWD is based on the replacement of the deficient or dysfunctional protein either by endogenous release from endothelial Weibel-Palade bodies or by administration of plasma-derived VWF concentrates. During the last years, several efforts have been made to optimize existing therapies for VWD, but also to devise new approaches, such as inducing endogenous expression with interleukin-11, administering exogenous recombinant VWF, or introducing the protein via gene delivery. Clearly, the efficacy of any strategy will depend on several factors, including, for example, the quantity, activity, and stability of the delivered VWF. The inherent complexity of VWF biosynthesis, which involves extensive posttranslational processing, may be limiting in terms of producing active VWF outside of its native cellular sources. This review summarizes recent progress in the development of different treatment strategies for VWD, including those that are established and those that are at the experimental stage. Potential pitfalls and benefits of each strategy are discussed.