NovoNordisk, Zurich Oerlikon, Switzerland.
Haemophilia. 2010 Mar;16 Suppl 2(0 2):24-7. doi: 10.1111/j.1365-2516.2009.02199.x.
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.
抑制剂的开发替代因子疗法是治疗血友病患者的严重并发症，需要使用旁路剂来防止不受控制的出血。重组因子 VIIa(rFVIIa)作为血友病患者旁路剂的疗效已在病例研究和临床试验中得到证实。然而，半衰期短和需要每天重复注射的认知意味着长期预防可能会受到限制。使用基因转移方法的犬血友病模型已被用于评估 FVIIa 在狗体内的持续表达。这些研究表明，可衡量的出血参数有所改善，这对血友病患者具有重要的临床意义。基因转移作为递送方法和 FVII 作为转基因的结合克服了 rFVIIa 半衰期短相关的问题，为血友病和其他血小板疾病患者的止血提供了一种有吸引力的新方法。
