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首页 » 帕金森病 » 帕金森患者的胚胎细胞疗法重新被提出

帕金森患者的胚胎细胞疗法重新被提出

来源:生物谷 2014-06-18 09:34

2014年6月18日讯 /生物谷BIOON/ --下个月,一个外科团队将在将夭折的人类胚胎移植进入帕金森患者的脑中,这个手术打破了长达十年之久的对帕金森患者治疗的停滞。在这之前对帕金森患者的治疗疗效甚微并且没有人能找到原因。之前有超过100名患者接受了这种治疗,但是由于治疗中心采用了不同的方法和过程,所以不能确定为什么有些患者的病情没有得到改善。

帕金森患者的神经细胞退化,使得神经细胞无法产生能在神经细胞传递的多巴胺,从而影响患者的行动,帕金森患者通常都无法自理生活。现有的治疗方法是采用药物L-dopa,来补充脑内的多巴胺,但是这种药物有很大的副作用。而现在的细胞治疗方法则是将已经退化的神经细胞用胚胎的脑细胞替换。

自2006年开始,7个负责移植脑细胞的科学团队重新聚集在一起,寻找其中的问题。他们发现,这种细胞治疗对于年轻病程短的患者更加有效,并且需要移植至少10万个细胞才能达到更好的疗效,而这些相当于3个婴儿的脑细胞的量。这样的分析使得科学家们重新开始了对这种治疗的尝试,他们将重新对150名患者进行尝试治疗,这些患者中,平均年龄不超过55岁,平均病程不超过4年,且没有任何人有L-dopa药物引发的运动障碍。

从2003年开始,干细胞的发展使得这样的治疗成为可能,由于胚胎的细胞来源很少并且生物差异很大,干细胞的发展将对于帕金森病症的细胞治疗起很大的促进作用。(生物谷Bioon.com)

详细英文报道:

Defective brain neurons are responsible for the mobility problems seen in people with Parkinson's disease.

A neurosurgery team will next month transplant cells from aborted human fetuses into the brain of a person with Parkinson's disease. The operation breaks a decade-long international moratorium on the controversial therapy that was imposed after many patients failed to benefit and no one could work out why.

But the trial comes just as other sources of replacement cells derived from human stem cells are rapidly approaching the clinic. And this time, scientists want to make sure that things go better. So the teams involved in all the planned trials have formed a working group to standardize their research and clinical protocols in the hope that their results will be more easily interpretable.

People with Parkinson's disease suffer from a degeneration of neurons that produce the neuro?transmitter dopamine, which is crucial for normal movement. This often leaves patients with severe mobility problems. Standard treatment includes the drug l-dopa, which replaces dopamine in the brain but can cause side effects. The cellular therapies aim to replace the missing neurons with dopamine-producing (dopaminergic) cells from fetal brains or with those derived from human stem cells.

The moratorium on replacement-therapy trials was introduced in 2003 because the early fetal-cell studies had produced varying results that were impossible to interpret.

"We want to avoid a repeat of this situation," says neurologist Roger Barker at the University of Cambridge, UK, who helped to organize the working group's inaugural meeting in London last month. The group, known as the Parkinson's Disease Global Force, includes scientists from the European, US and Japanese teams about to embark on the trials. At the meeting, they pledged to share their knowledge and experiences.

The first human transplantation of fetal brain cells took place in 1987 at Lund University in Sweden, where the technique was pioneered. Surgical teams took immature fetal cells destined to become dopaminergic neurons from the midbrain of aborted fetuses and transplanted them into the striatum of patients' brains, the area of greatest dopamine loss in Parkinson's disease.

More than 100 patients worldwide received the therapy as part of clinical trials before the moratorium. "But centres used different procedures and protocols - it was impossible to work out why some patients did very well and others didn't benefit at all," says Barker.

In 2006, Barker, together with neuroscientist Anders Bj?rklund at Lund University, set up a network to bring together the original seven teams that had performed the transplants, to assess all protocol details and patient data retrospectively.

The teams worked out that the procedure tended to be most effective in patients who were relatively young and whose disease was at an early stage. In addition, post-mortem analysis of patients' brains showed that those who benefited most had at least 100,000 dopamine-producing cells of fetal origin integrated into their brains. Cells from at least three fetuses are needed to achieve these numbers, the neuroscientists concluded.

The retrospective analysis encouraged the European scientists, including Barker and Bj?rklund, to launch a new trial, which is funded by the European Union, involving fetal dopaminergic-neuron transplants. Known as TRANSEURO, it will monitor disease progression in 150 patients in the United Kingdom, Sweden, France and Germany. The first patient is due for transplantation next month at Addenbrooke's Hospital in Cambridge. In line with the retro?spective findings, the average age of trial participants at recruitment was 55, and their average disease duration just 4 years. None had displayed dyskinesias - uncontrolled muscle movements that can be a side effect of l-dopa treatment.

But stem-cell biology has advanced significantly since 2003, and dopaminergic neurons can now be derived from human embryonic stem cells and also from induced pluripotent stem cells - mature cells that have been rewound to an uncommitted stem-cell-like state and that can be coaxed to become a cell type of choice. These potential sources are more desirable than those derived from fetuses, because fetal cells are hard to come by and their biology varies.

Research is under way to ensure that the stem cells develop into the exact type of dopaminergic cell needed to treat Parkinson's and that they become correctly integrated into recipients' brains. But progress has been so fast that clinical trials are already on the horizon. A Japanese trial, using induced pluripotent stem cells, is planned to start in Kyoto within two years; and two trials using human embryonic stem cells are also planned, one to begin within three years in New York and the other in Europe within four to five years.

The Parkinson's Disease Global Force hopes that its joint planning will make comparing outcomes easier. Members will share their protocols for deriving and grafting cells, as well as their clinical criteria for patient selection and follow-up.

They see the TRANSEURO trial as a pathfinder. "We don't know yet which source of cell will turn out to be the best, but right now the fetal cell is the gold standard we need to match," says neurologist Claire Henchcliffe from the Weill Cornell Medical Center in New York, who is coordinating the working group's guidelines on patient assessment and trial design.

The stem-cell approaches have a long way to go before they can rival the promise of fetal cells, says Lund University stem-cell biologist Malin Parmar, a member of the European clinical-trial team. That is because the cells from fetal brains are already on the way to becoming mature dopaminergic cells. "The human body knows very well how to develop each cell type from the embryo," she says. "We haven't learnt all of these secrets yet, but we have learnt some major ones."

 

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