四例血友病B患者基因治疗的临床试验  

The clinical trial of gene therapy on four hemophilia B patients

作　　者：邱信芳[1] 卢大儒[1] 王宏伟[1] 薛京伦[1] 杨健民[1] 孟沛霖[1] 

机构地区：[1]复旦大学,长海医院

出　　处：《复旦学报（自然科学版）》1996年第3期341-348,共8页Journal of Fudan University：Natural Science

基　　金：国家科委863高技术资助

摘　　要：报道了对四例血友病Ｂ患者基因治疗的临床试验，取自四例血友病Ｂ患者的自体皮肤成纤维细胞，通过反转录病毒介导的基因转移，能高效地分泌人凝血因子Ⅸ．用胶原包埋经遗传修饰的自体皮肤成纤维细胞，再移植到血友病Ｂ患者皮下．四例患者经治疗后，自发出血症状得到了减轻，血浆中凝血因子Ⅸ蛋白浓度和凝血活性明显地增加，其中两例患者增加较多，达到正常值的４％～５％．另外两例患者体内的凝血因子Ⅸ和凝血活性也有不同程度的提高．一例患者４００多天后经重复治疗，凝血因子Ⅸ浓度和凝血活性再次升高，持续至今已三年以上，临床治疗时和治疗后的随访中，均没有观察到复制型反转录病毒、恶性转化细胞及其他任何与治疗相关的副作用．试验结果表明：用经遗传修饰的分泌人凝血因子Ⅸ的皮肤成纤维细胞进行自体移植，为基因治疗血友病Ｂ提供了一简单而有效的途径．This paper deals with the clinical trial of gene therapy on four hemophilia B patients. Autologous skin fibroblasts from the patients trans feeted by retroviral vector are capable to express human clotting factor Ⅸ protein at a high level in vitro. Such genetically modified fibroblasts were embedded in collagen matrix and then transplanted subcutaneously in the patients. After treatment, bleeding of four patients was alleviated, and both concentration and bio-activity of clotting factor Ⅸ protein increased. In two cases the values reached to 4 %-5 % of the normal level, while the other two also increased in some extnts. 400 days later, one patient was treated again,the concentration and bio-activity of clotting factor Ⅸ protein in his plasma increased again, and remained thus for more than three years. No replication--competent retrovirus, malignant transformed cells and treatment-relative side effects were detected in this trial and follow-up evaluation. The result showed that autologously injection of genetically modified human skin fibroblasts could be a simple and feasible system of treatment on hemophilia B patients.

关 键 词：皮肤成纤维细胞 基因治疗 血友病B 

分 类 号：R554.105[医药卫生—血液循环系统疾病]