本帖最后由 开心之硕 于 2013-1-6 23:46 编辑
1# chinatiger
我自己翻译的，大家看看。说是iPS细胞在ＲＰ白鼠模型身上产生了长期的效果，基因疗法ＡＡＶ治疗Ｐｄｅ６α突变引起的ＲＰ也在白鼠身上产生了长期效果，但是并没有谈到人体试验以及与其的临床实验日期
2 Novel Treatments For Retinitis Pigmentosa Move Closer To Clinical Trials
两种新奇的RP治疗方法走近临床实验
Main Category: Eye Health / Blindness
Also Included In: Clinical Trials / Drug Trials
Article Date: 02 Jan 2013 - 0:00 PST
主分类：眼科健康/失明
亦包含于：临床实验/药物实验
文章日期：２０１３年１月２号
Two recent experimental treatments - one involving skin-derived induced pluripotent stem (iPS) cell grafts, the other gene therapy - have been shown to produce long-term improvement in visual function in mouse models of retinitis pigmentosa (RP), according to the Columbia University Medical Center (CUMC) scientists who led the studies. At present, there is no cure for RP, the most common form of inherited blindness.
根据哥伦比亚大学医学中心（CUMC）领导研究的科学家宣称，最近两项实验性治疗方式—一种是源于皮肤的IPS细胞，另一种是基因疗法—已经在RP老鼠模型中显示出长期的视力进步。目前为止，还没有治疗RP这种最普遍的遗传性失明的方法。
"While these therapies still need to be refined, the results are highly encouraging," said Stephen H. Tsang, MD, PhD, associate professor of pathology & cell biology and of ophthalmology at Columbia University Medical Center and an ophthalmologist at NewYork-Presbyterian Hospital/CUMC, the leader of both studies. "We've never seen this type of improvement in retinal function in mouse models of RP. We hope we may finally have something to offer patients with this form of vision loss."
“尽管这些疗法任然需要改进，但是结果很令人鼓舞” Stephen H. Tsang,博士说道，他是哥伦比亚大学医学中心眼科病理和细胞生物学的副教授，也是纽约医院的眼科专家，是这两项研究的主导人。“我们之前从没有在RP老鼠模型中见到过如此的视网膜功能进步。我们希望最终可以找到一些能提供给此类视野丧失的病人的疗法。”
The stem cell study was published in the journal Molecular Medicine. The gene therapy study was published in Human Molecular Genetics.
干细胞研究发表在《分子医学》期刊上。基因疗法发表在《人类分子基因学》上。
RP encompasses a group of inherited eye diseases that cause progressive loss of photoreceptor cells, specialized neurons found in the retina. While RP can appear during infancy, the first symptoms typically appear in early adulthood, beginning with night blindness. As the disease progresses, affected individuals lose peripheral vision. In later stages, RP destroys photoreceptors in the macula, which is responsible for fine central vision. Mutations in at least 50 genes have been found to cause the disease, which affects about 1.5 million people worldwide.
RP包含一系列遗传性的眼睛疾病，这些疾病将会引起进行性的视网膜上神经元—感光细胞的死亡。尽管在婴儿时期RP就出现，第一个典型的症状出现在成年早期阶段，即开始夜盲。随着疾病的进展，受影响的人将会失去周边视野。最后阶段，RP会损害黄斑上的感光细胞，黄斑负责精细的中心视野。至少50种基因的突变已经被发现能够引起RP，RP全世界大约影响了150万人。
In the Molecular Medicine study, the CUMC researchers tested the long-term safety and efficacy of using iPS cell grafts to restore visual function in a mouse model of RP. Like embryonic stem cells, iPS cells are "pluripotent" - that is, they are capable of developing into any cell type. However, iPS cells are not derived from embryos but from adult cells, in this case from human skin cells. The cells were administered, via injection directly underneath the retina, when the mice were five days old.
《分子医学》杂志上的这项研究，CUMC研究人员已经在老鼠模型测试了使用iPS移植修复视野功能的长期安全性和有效性，iPS细胞是“多功能性的”，这意味着它们可以发展成为任何形式的细胞。但是，iPS细胞并不是从胚胎中取得的，而是源于成体细胞，在这项研究中是来自于皮肤细胞。这些细胞在小白鼠5天大的时候，通过直接注射在视网膜眼底来管控。
The iPS cells assimilated into the host retina without disruption, and none of the mice receiving transplants developed tumors over their lifetimes, the researchers reported. The iPS cells were found to express markers specific to retinal pigmented epithelium (the cell layer adjacent to the photoreceptor layer), showing that they had the potential to develop into functional retinal cells. Using electroretinography, a standard method for measuring retinal function, the researchers found that the visual function of the mice improved after treatment and the effect was long lasting. "This is the first evidence of lifelong neuronal recovery in an animal model using stem cell transplants, with vision improvement persisting throughout the lifespan," said Dr. Tsang.
据研究者报导，这些iPS细胞同化成宿主细胞而没有产生破坏，没有一例接受移植的小白鼠在他们一生当中发展成肿瘤。iPS细胞被发现能作为RPE（毗邻于感光细胞层）的特殊产生体，通过使用电子视网膜图层（一种用来测试视网膜功能的标准方法），研究者发现小白鼠接受治疗后的视力提高是长期性的。“这是在动物模型中第一个证明用干细胞移植终生性的神经元恢复的例子，视力提高维持了终生。”Tsang博士说道。
In 2011, the FDA approved clinical trials of embryonic stem cell transplants for the treatment of macular degenerations, but such therapy requires immunosuppression. "Our study focused on patient-specific iPS cells, which offer a compelling alternative," said Dr. Tsang. "The iPS cells can provide a potentially unlimited supply of cells for functional rescue and optimization. Also, since they would come from the patient's own body, immunosuppression would not be necessary to prevent rejection after transplantation."
在2011年，FDA批准了胚胎干细胞移植治疗黄斑退化的临床实验，但是这项疗法需要抑制生物体自身的免疫反应。“我们的研究集中于病人 的iPS细胞，这是一项令人着迷的替换方法，”Tsang博士说道，“这些iPS细胞有潜力能为功能性恢复和优化提供无限的细胞支持。
In theory, iPS cell transplants could also be used to treat age-related macular degeneration, the leading cause of vision loss among older adults, said Dr. Tsang.
在理论上，iPS细胞移植也能够用于治疗老年性黄斑变性—这是老年人视野丧失的首要原因。”Tsang博士说道。
In the Human Molecular Genetics study, the CUMC researchers tested whether gene therapy could be used to improve photoreceptor survival and neuronal function in mice with RP caused by a mutation to a gene called phosphodiesterase-alpha (Pde6α) - a common form of the disease in humans. To treat the mice, the researchers used adeno-associated viruses (AAV) to ferry correct copies of the gene into the retina. The AAV were administered by a single injection in one eye, with the other eye serving as a control.
在《人类分子基因》的研究中，CUMC的研究者在患有由于Pde6α基因突变（这是人类ＲＰ中普遍的一种形式）的引起RP 的白鼠中证实了基因疗法能否用于治疗提高感光感光细胞的存活以及提高神经功能。为了治疗这些白鼠，研究人员运用ＡＡＶ病毒携带正常的基因模型到视网膜中，ＡＡＶ注射到一只眼睛中，另外一只眼睛作为样本。
When the mice were examined at six months of age (over one-third of the mouse lifespan), photoreceptor cells were found in the treated eyes but not in the untreated eyes, the researchers reported. More important, the treated eyes showed functional visual responses, while the untreated eyes had lost all vision.
研究人员报导，当白鼠在六个月后（超过白鼠的生命三分之一长度）进行检查，感光细胞在治疗过的眼睛中被发现，而在没有治疗的眼睛中并没有发现。更重要的是，接受治疗的眼睛显示出视力反应功能，而没有接受治疗的眼睛却完全失去了视野。
"These results provide support that RP due to PDE6α deficiency in humans is also likely to be treatable by gene therapy," said Dr. Tsang.
“这些结果提供了这样的证明，即人类中源于PDE6α缺陷引起的ＲＰ也可能通过基因疗法治疗。”ＴＳａｎｇ博士说道。 |
