Grossman M, Raper S E, Wilson J M
Department of Internal Medicine, Howard Hughes Medical Institute, Ann Arbor, MI 48109.
Hum Gene Ther. 1992 Oct;3(5):501-10. doi: 10.1089/hum.1992.3.5-501.
Ex vivo gene therapy directed to the liver is being developed for the treatment of inherited metabolic diseases. Transplantation of hepatocytes that have been transduced with a low-density lipoprotein (LDL) receptor gene is a potential form of therapy for familial hypercholesterolemia (FH). We have demonstrated efficacy of ex vivo gene therapy for familial hypercholesterolemia in a rabbit animal model of this disease. In preparation for human trials, we describe in this report experiments in baboons for documentation of the feasibility and safety of autologous hepatocyte transplantation. Three baboons underwent a partial hepatectomy and their hepatocytes were isolated, cultured, and transduced with a retrovirus containing the human LDL receptor gene. The hepatocytes were harvested and infused into an indwelling catheter that had been placed into the inferior mesenteric vein at the time of liver resection. The baboons tolerated the procedures well and are being maintained and clinically evaluated for an indefinite time period. Follow-up evaluations have ranged from 3 to 8 months. Clinical evaluations have been unremarkable and blood chemistry and hematology determinations have stayed within normal limits.
针对肝脏的离体基因治疗正在开发用于治疗遗传性代谢疾病。用低密度脂蛋白（LDL）受体基因转导的肝细胞移植是家族性高胆固醇血症（FH）的一种潜在治疗形式。我们已经在这种疾病的兔动物模型中证明了离体基因治疗家族性高胆固醇血症的有效性。为准备人体试验，我们在本报告中描述了在狒狒身上进行的实验，以证明自体肝细胞移植的可行性和安全性。三只狒狒接受了部分肝切除术，分离、培养了它们的肝细胞，并用含有人类LDL受体基因的逆转录病毒进行转导。收获肝细胞并将其注入在肝切除时已放置在下肠系膜静脉的留置导管中。狒狒对这些操作耐受性良好，并将被无限期维持和进行临床评估。随访评估时间为3至8个月。临床评估无异常，血液化学和血液学测定结果保持在正常范围内。
