地中海貧血癥患者往往要靠定期輸血來保持健康,，而一個(gè)國(guó)際科研小組日前報(bào)告說，其開展的以基因療法治療一名地中海貧血癥患者的試驗(yàn)取得初步成功,。這名患者已不再需要輸血,，并擁有一份正常的工作。
法國(guó),、美國(guó),、意大利等國(guó)科研人員在新一期英國(guó)《自然》雜志上報(bào)告說,，這名男性患者從3年前開始接受基因療法,。當(dāng)時(shí)他18歲，患有β型地中海貧血癥,。這種病由基因缺陷引起,，患者自身不能生成正常的紅細(xì)胞，因此需要通過輸血來保持血液的供養(yǎng)等功能,。這名患者從3歲開始輸血,，嚴(yán)重時(shí)每個(gè)月都要輸血。
在基因療法試驗(yàn)中,，研究人員先利用患者自身的骨髓造血干細(xì)胞培養(yǎng)出包括紅細(xì)胞在內(nèi)的血液細(xì)胞,，然后使用病毒作載體，將無缺陷的基因引入這些細(xì)胞中,，再用化學(xué)手段去除多余細(xì)胞,，只留下基因缺陷得到修正的紅細(xì)胞,，最后將這些紅細(xì)胞移植回患者體內(nèi)。
結(jié)果顯示,，患者自身生成正常紅細(xì)胞的能力逐漸上升,，在接受治療一年后就不再需要輸血了。現(xiàn)在該患者雖然仍有輕微貧血癥狀,，但迄今一直不需要輸血,，并且已經(jīng)有了一份全職的廚師工作，這說明基因療法取得了初步成功,。
不過也有專家對(duì)這一結(jié)果持謹(jǐn)慎態(tài)度,，比如認(rèn)為試驗(yàn)成功與這名患者自身的一些生理特點(diǎn)有關(guān)，可能難以在其他患者身上復(fù)制成功經(jīng)驗(yàn),。試驗(yàn)中使用的病毒帶來了一定的副作用,，有引發(fā)癌癥的可能。但是總的來說,，這次試驗(yàn)打開了使用基因療法治療地中海貧血癥的大門,，為許多患者帶來了希望。
據(jù)研究者介紹,，β型地中海貧血癥多見于地中海地區(qū)和東南亞?，F(xiàn)有治療手段除了定期輸血外，還有移植造血干細(xì)胞等,，但通常很難找到匹配的干細(xì)胞捐獻(xiàn)者,，因此基因療法成為一個(gè)新的研究方向。（生物谷Bioon.com）
生物谷推薦英文出處：
Nature 467, 318-322 (16 September 2010) | doi:10.1038/nature09328; Received 27 January 2010; Accepted 28 June 2010
Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia
Marina Cavazzana-Calvo1,2,17, Emmanuel Payen3,4,5,17, Olivier Negre3,4,5,6, Gary Wang7, Kathleen Hehir8, Floriane Fusil3,4,5, Julian Down8, Maria Denaro8, Troy Brady7, Karen Westerman8,9, Resy Cavallesco9, Beatrix Gillet-Legrand6, Laure Caccavelli1,2, Riccardo Sgarra10, Leila Maouche-Chrétien3,4, Fran?oise Bernaudin11, Robert Girot12, Ronald Dorazio8, Geert-Jan Mulder8, Axel Polack8, Arthur Bank13, Jean Soulier5, Jér?me Larghero5, Nabil Kabbara5, Bruno Dalle5, Bernard Gourmel5, Gérard Socie5, Stany Chrétien3,4,9, Nathalie Cartier14, Patrick Aubourg14, Alain Fischer1,2, Kenneth Cornetta15, Frédéric Galacteros16, Yves Beuzard3,4,5, Eliane Gluckman5, Frederick Bushman7, Salima Hacein-Bey-Abina1,2,17 & Philippe Leboulch3,4,9,17
The β-haemoglobinopathies are the most prevalent inherited disorders worldwide. Gene therapy of β-thalassaemia is particularly challenging given the requirement for massive haemoglobin production in a lineage-specific manner and the lack of selective advantage for corrected haematopoietic stem cells. Compound βE/β0-thalassaemia is the most common form of severe thalassaemia in southeast Asian countries and their diasporas1, 2. The βE-globin allele bears a point mutation that causes alternative splicing. The abnormally spliced form is non-coding, whereas the correctly spliced messenger RNA expresses a mutated βE-globin with partial instability1, 2. When this is compounded with a non-functional β0 allele, a profound decrease in β-globin synthesis results, and approximately half of βE/β0-thalassaemia patients are transfusion-dependent1, 2. The only available curative therapy is allogeneic haematopoietic stem cell transplantation, although most patients do not have a human-leukocyte-antigen-matched, geno-identical donor, and those who do still risk rejection or graft-versus-host disease. Here we show that, 33 months after lentiviral β-globin gene transfer, an adult patient with severe βE/β0-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21?months. Blood haemoglobin is maintained between 9 and 10?g?dl?1, of which one-third contains vector-encoded β-globin. Most of the therapeutic benefit results from a dominant, myeloid-biased cell clone, in which the integrated vector causes transcriptional activation of HMGA2 in erythroid cells with further increased expression of a truncated HMGA2 mRNA insensitive to degradation by let-7 microRNAs. The clonal dominance that accompanies therapeutic efficacy may be coincidental and stochastic or result from a hitherto benign cell expansion caused by dysregulation of the HMGA2 gene in stem/progenitor cells.
