德国:特殊骨髓干细胞移植或可治疗艾滋病
http://www.huanqiu.com 来源:39健康网 2009-02-15 13:55
据《自然》网站报道,一名患艾滋病和白血病的男子在接受特殊干细胞移植手术后,两种疾病均被“治愈”。移植所用干细胞来源于一位对艾滋病具有先天免疫力的捐赠者。现在2年时间过去了,即使该名患者没有使用抗逆转录病毒药品,也没有再发现HIV病毒。
德国医生在2008年11月就曾公布了他们的发现,从那时起,研究结果经过了同行评议并最终发表在了著名的《新英格兰医学杂志》(NewEngland Journal of Medicine)上。
任何对化疗反应不佳的白血病患者都应接受骨髓移植,医生会搜寻骨髓捐赠者的注册资料,来为病人寻找合适配型,并准备进行移植手术。
不过德国柏林夏瑞蒂医学院(Charité Universittsmedizin)血液学家Gero Hütter所做的工作比一般的骨髓移植又进了一步,Hütter并不是专攻艾滋病的学者,但是当他意识到他的一位病人需要进行骨髓移植时,他想起10年多以前他曾读过的一篇论文,讲的是一些人具有特殊的遗传变异,使他们对艾滋病具有抵抗力。
这种变异是指CCR5基因上一小段缺失。这一基因编码了一个受体,艾滋病毒利用这个受体来侵入称为CD4+ T细胞的免疫细胞。有大约1%的欧洲人口其CCR5基因的全部2个拷贝有这种变异,这使得这些人很难感染艾滋病毒。如果Hütter能用这种缺少CCR5受体的细胞替代病人免疫细胞的话,病人也许就不会那么容易感染艾滋病毒了。
Hütter在德国骨髓捐献中心为这名病人找到了80个合适的配型,其中61号骨髓捐献者被证实具有这种CCR5变异,在2007年2月Hütter对患者进行了这一移植手术。
美国宾夕法尼亚大学艾滋病研究者James Riley表示,尽管到现在为止只做了一例这种手术,不过结果是极具价值的。他说:“这提供了充足证据表明,如果让身体中大部分细胞具有对艾滋病的抵抗力,则身体真的能够抵抗病毒。”
Hütter则表示另一组医生正准备对另一名艾滋病测试阳性的白血病病人进行同样的手术,这将是第二例这种手术,几年后我们就能看到结果。
那么患者究竟有没有被治愈呢?这还说不好,尽管该名患者大约2年时间没有出现复发,不过有可能病毒仍然会回来。病毒也许正潜伏在医生无法检验的细胞内,比如脑部或心脏的细胞。
此外,还有一类艾滋病毒并不利用CCR5受体来侵入细胞。这类病毒通常不会在有正常免疫系统的病人身上出现,不过它们可能最终会在这名病人体内繁衍。
可以确定的是,大多数艾滋病测试阳性的人恐怕不会愿意接受这种治疗方法。骨髓移植有一定风险,相比数年的抗逆转录病毒药物疗法来说,即使考虑到药物的副作用,骨髓移植的风险还是要更大一些。在接受骨髓移植前,病人要接受药物和放射处理来杀死自己的造血干细胞,这一过程中,病人极易受到感染,并且最终病人的身体还有可能对所移植的干细胞产生排异。
有一些药物可以起到类似的作用,美国辉瑞制药公司所生产的一种CCR5抑制剂,称为maraviroc,已被批准在美国和欧洲使用。其他公司则忙于研发更进一步的靶向CCR5的药品。
不幸的是,maraviroc并不能完全阻止艾滋病毒绑定到CCR5,而且这种药得与其它抗逆转录病毒药品一起组合使用。Riley表示:“基本上艾滋病毒能找到一些方法绕过药物而继续利用CCR5”,他还补充说,艾滋病毒可能能击败抑制药物,或者能绑定到CCR5的其他部分,而药物却不行。
其他研究人员正在试验基因疗法来完全阻止CCR5的产生。比如,Riley过去曾与一家称为Sangamo BioSciences的生物技术公司合作,以确定该公司一种用于敲除目标基因的技术是否能用于敲除CCR5基因。Sangamo公司上周宣布,公司已经开始临床I期试验,这一试验将包括移出参与者T细胞的一个样本,敲除CCR5基因,并且最后将这一改动过的细胞重新注入病人体内。这一试验是搞清该类技术安全性而非疗效的第一步,并且参与者的未受改动的T细胞将不会被摧毁。
http://www.huanqiu.com Source: 39 Health Net 2009-02-15 13:55
According to "Nature" Web site reported that a risk of AIDS and leukemia in men receiving special stem cell transplantation surgery, the two diseases are "cured." Transplantation using stem cells derived from one pairs of innate immunity with AIDS donors. Now 2 years have passed, even if the patients did not use anti-retroviral drugs, has not found HIV virus.
Doctor in Germany in November 2008 had announced their discovery, from then on, the results have been peer-reviewed and eventually published in the famous "New England Journal of Medicine" (NewEngland Journal of Medicine) on.
Any poor response to chemotherapy in patients with leukemia should be subject to a bone marrow transplant, doctors will search for bone marrow donor register information, to find the appropriate matching of patients and preparation for transplant.
But Germany柏林夏Morante Medical School (Charité Universittsmedizin) scientist Gero Hütter blood work done than the average bone marrow transplant also goes a step further, Hütter is not a scholar specializing in AIDS, but when he realized one of his patients required a bone marrow transplant, he think of more than 10 years ago he had read a paper, some people are talking about a special genetic variation, so that they have a resistance to AIDS.
This variability means that a small deletion on the CCR5 gene. This gene encodes a receptor, the HIV receptor to make use of this invasive called CD4 + T cells in immune cells. Has around 1% of Europe's population of all of its CCR5 gene has two copies of this variant, which makes them difficult to HIV infection. If Hütter use this lack of CCR5 receptor cell replacement patients immune cells, then the patient might not be so vulnerable to HIV infection has.
Hütter bone marrow donation center in Germany for this patient found 80 matching suitable, of which 61 bone marrow donors was confirmed with this CCR5 mutation, in February 2007 on patients with Hütter the transplant.
PA American University AIDS researcher James Riley said that although up to now only one case of such a surgery, but the results are valuable. He said: "This provides ample evidence that most of the body cells of resistance to AIDS, the body really be able to resist the virus."
Hütter, said another group of doctors are ready to test another HIV-positive patients with leukemia the same operation, this will be the second case of this surgery, a few years we will be able to see the result.
Well, what patients have not been cured? This also bad, although the patients were around 2 years without recurrence, but may have the virus still will return. Virus may be hidden in the doctor can not test the cells, such as brain or heart cells.
In addition, there is one type of HIV is not the use of CCR5 receptor to invasive cells. Such viruses usually do not have normal immune system in patients who appear, though they may eventually be in the in vivo proliferation of this patient.
To be sure, the majority of AIDS in people who test positive will probably not willing to accept such treatment. Bone marrow transplantation has certain risks, compared to several years of antiretroviral drug therapy, even taking into account the drug's side effects, the risk of bone marrow transplantation or larger. In bone marrow transplant before the patient to accept the drugs and radiation treatment to kill their own hematopoietic stem cells, this process, the patient vulnerable to infection and, ultimately, the patient's body may be of the transplanted stem cells produce rejection.
Has a number of medicines can play a similar role in the United States by Pfizer pharmaceutical company producing a CCR5 inhibitor, known as maraviroc, has been approved in the United States and Europe. Other companies are busy with further research and development of drugs targeting CCR5.
Unfortunately, maraviroc can not completely prevent HIV binding to CCR5, and this drug was with other antiretroviral drugs used in combination together. Riley said: "HIV is basically to find some way to bypass the drug and continue to use CCR5", he added, HIV may be able to beat the inhibitory drugs, or can bind to other parts of CCR5, and the drugs can not.
Other researchers are experimenting with gene therapy to fully prevent the emergence of CCR5. For example, Riley has called Sangamo BioSciences with a biotechnology company to identify the company a target for gene knock-out to see whether the technology can be used CCR5 gene knockout. Sangamo, announced last week that the company has begun Phase I clinical trial, the trial moved out of the participants will include a sample of T cells, CCR5 gene knockout, and the final will be the altered cells to re-inject patients. This test is to understand the safety of such techniques rather than the efficacy of the first step, and participants were not altered T cell will not be destroyed.
[1]