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Nature:干细胞移植可清除HIV病毒     [复制链接]

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楼主
发表于 2013-7-4 21:08 |只看该作者 |倒序浏览 |打印
Nature:干细胞移植可清除HIV病毒' H. J' v3 h# y+ s- ^
2013-07-04 来源:生物360 作者:koo
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“波士顿病人”在停止艾滋病药物治疗后未复发
# r  h; D3 O3 T2 I9 _近日,两名艾滋病患者在接受骨髓移植后停止了药物治疗,据医生称,患者体内的病毒似乎已消除。
, t+ s! P9 t; [9 B0 D' z其中一名患者在停药近四个月后,也没有任何疾病重返的症兆。( I5 ]3 V/ j: W5 J; M3 t
然而来自美国布莱根妇女医院的研究团队提醒称,目前得出艾滋病治愈的结论仍为时过早,因为病毒可能随时重返人体。
& t( }# |6 d" Q艾滋病毒在侵入人体后,会极大地破坏人体的免疫机能。艾滋病毒会融合于人体细胞的DNA,一经感染,就很难完全摆脱。
8 I% |0 T+ z$ X$ e' \( K( E( v+ V尽管抗逆转录病毒药物能使人体血液系统中的病毒得到控制,但一旦药物停用,病毒会卷土重来。3 Z" B3 F. ]1 p6 F/ x/ V
艾滋病治愈?1 b) b1 [3 g0 L' G% {
两名未透露身份的艾滋病患者感染艾滋病毒已有三十年。
4 N; q+ l1 |1 C: w4 u: Y他们都继发了淋巴癌,需要接受骨髓移植手术。
9 v+ K( `, h+ e0 P8 Q5 j0 o% d骨髓是人体的造血组织,其功能是产生人体所需的血细胞。它也被认为是艾滋病毒在人体内的主要“藏身之处”。
& j: D8 v) @( ~+ l. e2 p接受移植手术后,一名患者血液中两年未检测到艾滋病毒,而另一名则长达四年。6 n0 H- C3 t# i3 k* E2 o- L' g
他们两人都于今年年初停止服用抗逆转录病毒药物,到目前没有检测到任何病毒“死灰复燃”的迹象。
3 \2 v1 _; R/ Z6 k% U7 \7 T蒂莫西•亨里奇医生(Timothy Henrich)告诉BBC,这是一个振奋人心的结果,但他同时补充道,“我们尚未证实这能够完全治愈艾滋病,还需要更长时间的观察和追踪。”+ V) z! S# Y7 p6 \) @) S: r
“但我们能够肯定的是如果在停止药物治疗一到两年时间内,没有检测到病毒,病毒重返人体的几率就非常低。”
* o: L  e+ c' L& `, C# k, Z; u- |然而据亨里奇医生称,艾滋病毒仍可能潜伏在患者的脑组织或胃肠道中。" ^1 c3 h; ^' U( s
“一旦病毒重返人体,则表明这些组织也是病毒重要的聚集地,在未来艾滋病治疗方案的探索中需要对此开展新的研究。”& V3 P+ k, Q' y( ]
柏林病人
! d3 t) a; L" C8 N! M蒂莫西• 布朗(Timothy Brown),也被称为“柏林病人”,被认为是通过骨髓移植治愈了艾滋病的第一人。他接受了一名存在罕见基因突变的捐赠人的骨髓,这种突变使其可抵御艾滋病毒。
/ w; `3 S, t9 ]而在上述两个来自美国的成功案例中,患者接受的都是普通捐赠人的骨髓。
( x8 B: g3 f  s" ~& b! _在美国密西西比州还有一个携带艾滋病毒的婴儿被成功治愈的案例。她自出生起便开始接受抗逆转录病毒药物治疗。分析称,抗逆转录病毒药物很可能在病毒库形成以前就已将病毒消除。
/ c+ [1 k3 D# n( s2 j" V* ^0 n7 [% Z来自泰伦斯•席金斯基金会(Terrence Higgins Trust)的迈克•布雷迪医生(Michael Brady)表示,现在尚不能得出结论那两名美国患者体内的病毒是否已永久地消除了,但这一案例显示,此前在“柏林病人”身上发生的情况看来是并非偶然的。+ ?& w5 F% w0 y6 J# x
布雷迪医生说,“骨髓移植是非常复杂和昂贵的治疗手段,而且伴有重大风险。对多数艾滋病患者而言,每日接受药物治疗控制病毒的风险远比接受骨髓移植要低的多。”
5 j$ }  P( D  Y" v4 E5 D“尽管这未必是一个行的通的治疗方案,骨髓移植仍然给研究人员指明了一个新的方向。”
: r! l2 a; g4 j/ `- m艾滋病研究基金会主席凯文•弗洛斯特(Kevin Frost)表示,这些研究成果提供了新的重要信息,而这些信息将极大地改变人们对艾滋病和基因疗法的思维。
& s* Z! R& j; F& n. ]* [: N“由于干细胞移植的复杂程度和高昂费用,这一治疗方案并不适用于广大的艾滋病患者。但这些案例将引领我们走上治疗并可能最终消除艾滋病的新路径。”
9 z* \/ x; h; B! Z9 |延伸阅读:/ |6 t* `6 l0 c8 L( A
美国研究人员宣称首次治愈艾滋患儿0 u4 M: S8 p( |2 O# k; I; H
早期干预亦能“功能性治愈”成年人的HIV感染
2 x6 v/ x, r* o) ?治愈艾滋病具有现实可能性——HIV发现者谈人类抗艾30年
$ ^" B4 }3 L( C原文检索:
) k5 X- H! G/ \( NErika Check Hayden. Stem-cell transplants may purge HIV. Nature, 03 July 2013; doi:10.1038/nature.2013.13297. q* ]9 o2 s7 \/ J' M! b: \+ U
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沙发
发表于 2013-7-4 22:35 |只看该作者
期盼攻克难题的一天
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藤椅
发表于 2013-7-5 10:52 |只看该作者
干细胞在抗病毒方面的研究似乎不太多,这个研究很振奋人心啊,不知其他病毒感染比如HBV等DNA病毒是否也有望用应用干细胞来治疗
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发表于 2013-7-5 11:15 |只看该作者
干细胞之家微信公众号
HIV干细胞治疗的突破给众多感染者带来了希望。加之这两例的成功,从一定意义否定了之前“柏林病人”的成功治愈被认为是个例的共识。目前NK细胞也被发现在HIV携带者、AIDS病人和正常人中有不同的亚群的存在,而通过相应亚群NK细胞特异性杀伤HIV感染的CD4 cell而保护正常未被感染的CD4 cell,辅助抗病毒治疗,也可能是另一种更为低成本和可能性更高的抗病毒和免疫重建的方法。
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发表于 2013-7-5 12:33 |只看该作者
然而据亨里奇医生称,艾滋病毒仍可能潜伏在患者的脑组织或胃肠道中。难道HIV不仅只是感染免疫相关细胞,还能感染非免疫细胞?
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发表于 2013-7-5 16:07 |只看该作者
回复 zhouleiwang2 的帖子! f) q1 `- S! M
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HIV是可以跨过血脑屏障的,但是很多药物无法跨过,这也是很多药物效果有限的重要原因,感染HIV后,病毒可以潜伏在脑组织中。
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发表于 2013-7-5 22:33 |只看该作者
回复 bin 的帖子  c# a& o+ K' t+ I+ x1 H; j/ P* J& v
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原来如此 ,谢谢版主。追问:HIV的感染据说需要两个受体CD4和CCR5或者CXCL4,HIV在脑内是只存在于细胞外吗?还是说某些神经细胞也可以表达上述受体的同源物而被HIV潜伏?
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发表于 2013-7-6 01:02 |只看该作者
看到这篇新闻,表示兴奋,期待继续深入研究。

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发表于 2013-7-6 01:12 |只看该作者
仅仅是移植了骨髓的作用?  干细胞起到了什么作用?增强免疫?
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发表于 2013-7-6 01:16 |只看该作者
原文如下:
2 g+ m0 G; g8 T/ N! s# NTwo men with HIV may have been cured after they received stem-cell transplants to treat the blood cancer lymphoma, their doctors announced today at the International AIDS Society Conference in Kuala Lumpur.' H5 Q6 E! f/ R4 |, p* z

. f* v4 E3 g2 jOne of the men received stem-cell transplants to replace his blood-cell-producing bone marrow about three years ago, and the other five years ago. Their regimens were similar to one used on Timothy Ray Brown, the 'Berlin patient' who has been living HIV-free for six years and is the only adult to have been declared cured of HIV. Last July, doctors announced that the two men — the ‘Boston patients’ — appeared to be living without detectable levels of HIV in their blood, but they were still taking antiretroviral medications at that time.
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Timothy Henrich, an HIV specialist at Brigham and Women’s Hospital in Boston, Massachusetts, who helped to treat the men, says that they have now stopped their antiretroviral treatments with no ill effects. One has been off medication for 15 weeks and the other for seven. Neither has any trace of HIV DNA or RNA in his blood, Henrich says.& j* H  p, P5 i9 o; `
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If the men stay healthy, they would be the third and fourth patients ever to be cured of HIV, after Brown and a baby in Mississippi who received antiretroviral therapy soon after birth.: i) v, |5 j1 j7 P

- c0 G# p5 n6 c; n8 oBut Henrich and Daniel Kuritzkes, a colleague at Brigham who also worked with the men, caution that it is still too early know whether or not the Boston patients have been cured. For that, doctors will need to follow the men closely for at least a year, because the virus may be hiding out in 'reservoirs' — parts of the men’s bodies, such as their brain or gut, that can harbour the virus for decades.
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# A, W0 a, M- Z% [2 K“We’re being very careful not to say that these patients are cured,” Kuritzkes says. “But the findings to date are very encouraging.”! g! R7 L& i2 W# {( y& @1 i
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HIV researcher Steven Deeks of the University of California, San Francisco, says that doctors might need to wait at least two years before declaring that a cure has been achieved. “Any evidence that we might be able to cure HIV infection remains a major advance,” Deeks says. But, he adds, “there have been cases of patients who took many weeks off therapy before the virus took off”.
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. R' }/ I( \2 z9 K4 o! HExciting news! _5 F; A4 N/ {( t
Still, researchers and doctors are excited about the news, especially because the Boston patients’ treatment differed from the Berlin patient’s regimen in one key way. Brown was given stem cells that were predisposed to resist HIV infection, because the donor happened to have a mutated version of a key protein — CCR5 — that is needed for HIV to infect cells. So Brown’s transplant was akin to gene therapy with HIV-resistant cells.
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2 e. r3 r. h4 {+ q8 G7 |! {But the Boston patients received stem cells without the protective mutation. The transplanted cells must therefore have been protected from infection by the antiretroviral drugs taken during cancer treatment. Their doctors think that an immune response called graft-versus-host disease — a post-transplant reaction in which donated cells kill off a patient’s own cells — may have then wiped out the patients’ HIV reservoirs, potentially curing the men.% J% P- E" n+ X9 v. \

: |" z, B( n+ {; x1 i, O# {Transplant specialist Christine Durand of Johns Hopkins University School of Medicine in Baltimore, Maryland, says that the case of the Boston patients may show that current antiretroviral drugs are powerful enough, on their own, to protect the transplanted cells. “If cure has been achieved in the Boston patients, then it was the antiretroviral therapy, not gene therapy, that protected the donor cells,” she says.4 G7 }7 R! U  q: n

. `; W5 p0 J$ t0 R& F' _The finding is very important for people with HIV who also need blood-cell transplants, but the treatment is unlikely to be used more generally because the risks from transplants are high. Durand says that Johns Hopkins is now revising its transplant procedures to keep people with both cancer and HIV on antiretroviral drugs during the transplant regimen.9 a- B) Z1 G0 z
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Separately, the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, based in Silver Spring, Maryland, is trying to replicate the Berlin patient’s cure by giving CCR5-mutated HIV-resistant blood from umbilical cords to children and adults with HIV and cancer. * e5 {( t( p  `% d" Q
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Everyone with HIV could benefit from this work, researchers say, because it could yield valuable information about how to eliminate the HIV reservoir.
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4 ?- W1 }% M/ R* S, h- S“We are still a long way off from a viable cure option for most patients,” Durand says. “But every step counts, and these cases can teach us important lessons.
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