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有读书笔记Efficacy of gene therapy for X-linked severe combined immunodeficiency

聚焦生物 添加于 2010-8-5 22:31 | 1367 次阅读 | 0 个评论

  •  作 者

    Hacein-Bey-Abina S, Hauer J, Lim A, Picard C, Wang GP, Berry CC, Martinache C, Rieux-Laucat F, Latour S, Belohradsky BH, Leiva L, Sorensen R, Debre M, Casanova JL, Blanche S, Durandy A, Bushman FD, Fischer A, Cavazzana-Calvo M

  •  摘 要

    BACKGROUND: The outcomes of gene therapy to correct congenital immunodeficiencies are unknown. We reviewed long-term outcomes after gene therapy in nine patients with X-linked severe combined immunodeficiency (SCID-X1), which is characterized by the absence of the cytokine receptor common gamma chain. METHODS: The nine patients, who lacked an HLA-identical donor, underwent ex vivo retrovirus-mediated transfer of gamma chain to autologous CD34+ bone marrow cells between 1999 and 2002. We assessed clinical events and immune function on long-term follow-up. RESULTS: Eight patients were alive after a median follow-up period of 9 years (range, 8 to 11). Gene therapy was initially successful at correcting immune dysfunction in eight of the nine patients. However, acute leukemia developed in four patients, and one died. Transduced T cells were detected for up to 10.7 years after gene therapy. Seven patients, including the three survivors of leukemia, had sustained immune reconstitution; three patients required immunoglobulin-replacement therapy. Sustained thymopoiesis was established by the persistent presence of naive T cells, even after chemotherapy in three patients. The T-cell-receptor repertoire was diverse in all patients. Transduced B cells were not detected. Correction of the immunodeficiency improved the patients' health. CONCLUSIONS: After nearly 10 years of follow-up, gene therapy was shown to have corrected the immunodeficiency associated with SCID-X1. Gene therapy may be an option for patients who do not have an HLA-identical donor for hematopoietic stem-cell transplantation and for whom the risks are deemed acceptable. This treatment is associated with a risk of acute leukemia. (Funded by INSERM and others.)

  •  详细资料

    • 文献种类:期刊
    • 期刊名称: The New England Journal of Medicine
    • 期刊缩写: N Engl J Med
    • 期卷页: 2010年  第363卷 第4期 355-364页
    • 地址: Department of Biotherapy, Necker-Enfants Malades Hospital, Paris, France. salima.hacein-bey@nck.ap-hop-paris.fr
    • ISBN: 0028-4793
    • 备注:PMID:20660403

  • 相关链接 DOI URL 

  •  聚焦生物 的文献笔记  订阅

    基因疗法治疗“气泡男孩症”

    “气泡男孩症”的病因是X染色体发生了严重的化合免疫缺陷，患者只能在完全无菌的条件下生存。这种疾病是由于基因突变干扰了淋巴细胞的正常数量，只 有男孩会遗传该基因，患者没有淋巴细胞，所以无法抵抗传染病，只能生活在类似气泡那样被完全隔离起来的无菌环境里，即便对普通人而言并不严重的感染，对患 有此病的人来说也可能是致命的。据统计，在5万～10万个新生儿中，至少有一个婴儿患此病。

    据美国权威期刊《新英格兰医学杂志》7月22日报道，法国巴黎内克尔儿童医院的研究人员从1999年开始，对平均7个月大的9名男婴实施基因疗法，在9年后，1名男孩因患白血病死去，其他8名都健康地活着。今年，这8名男孩的淋巴细胞水平都达到了正常，体重和身高并未停止增长，甚至可以像其他正常的孩子一样去上学。不过，这种疗法的最大副作用就是可能导致白血病，幸存8人中有3人患有白血病。

    美国纽约罗切斯特大学神经病学副教授威廉·鲍尔说，这已经是非常了不起的进步了。此前治疗“气泡男孩症”的方法只有骨髓移植，但这需要相匹配的捐赠者，而且会导致严重的并发症。从1999年到2002年间，医学专家在修正基因的病毒载体方面取得了重大进展，接受基因治疗的9个男婴由于没有匹配的骨髓捐赠者，只能将自身骨髓中的一种干细胞取出，注入修正基因后再注射到患者体内，结果他们当中没有一个出现严重反应。鲍尔副教授说，这些成果证实，基因疗法在治疗“气泡男孩症”方面已取得了临床上的成功。

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