Animal models of FVIIa gene expression: their role in the future development of haemophilia treatment.

The development of inhibitors to replacement factor therapy is a serious complication in the treatment of patients with haemophilia and requires use of bypassing agents to prevent uncontrolled bleeding. The efficacy of recombinant factor VIIa (rFVIIa) as a bypassing agent in patients with haemophilia has been demonstrated in case studies and clinical trials. However, the perception of a short plasma half-life and consequent need for repeated daily injections means that long-term prophylaxis could potentially be limiting. Canine haemophilia models using a gene transfer approach have been used to evaluate the continuous expression of FVIIa in dogs. These studies show improvement in measurable bleeding parameters that have important clinical ramifications for patients with haemophilia. The combination of gene transfer as the method of delivery and FVII as the transgene overcomes issues associated with the short plasma half-life of rFVIIa, and represents a potentially attractive novel approach to haemostasis in patients with haemophilia and other platelet disorders.