帕金森氏病患者移植的脑细胞能成活数年

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Parkinson's brain cell transplants last for years
Sun Apr 6, 2008 1:21pm EDT

By Maggie Fox, Health and Science Editor

WASHINGTON (Reuters) - Transplants of brain cells given to Parkinson's disease patients survive for 10 years or more, three teams of researchers reported on Sunday, but at least some of the transplants were damaged.

The researchers disagree about whether this damage shows that Parkinson's disease is a long-term, ongoing process that continues to attack the brain into old age, or the result of the transplants themselves.

But they agree that their studies, published in the journal Nature Medicine, demonstrate the benefits of the sometimes controversial brain cell transplants.

\"I think these findings lend much optimism to future work,\" said Dr. Ole Isacson of McLean Hospital and Harvard Medical School in Massachusetts, who worked on one of the studies.

Parkinson's disease, which affects more than a million patients in the United States alone, is marked by the death of brain cells that produce dopamine, a message-carrying chemical associated with movement. Drugs can delay symptoms for a while but there is no good treatment and no cure.

Patients report shakiness, which progresses to paralysis and sometimes dementia and death.

A few teams tried transplanting brain cells, some from aborted fetuses, to replace cells destroyed by the disease.

Jeffrey Kordower of Rush University Medical Center in Chicago and colleagues described the case of a 61-year-old woman who died 14 years after she got a transplant.

She initially got better but then deteriorated until she died. Her brain showed signs of damage similar to that caused by Parkinson's, Kordower's team reported.

\"This case reveals that pathological changes typical of Parkinson's disease can develop in human fetal neurons grafted into a host with Parkinson's disease,\" they wrote.

ONGOING PROCESS?

Patrik Brundin of Wallenberg Neuroscience Center in Lund, Sweden, and colleagues found some damage to cells transplanted into the brains of patients. But they said the transplants had survived for as long as 16 years and the patients had reported relief from their symptoms.

Kordower believes the findings suggest that Parkinson's is caused by an ongoing process that lasts for years. \"Whatever the offending agent is, it is still present in the Parkinson's brain,\" he said in a telephone interview.

He said only about 5 percent of the cells were damaged.

\"If you ask me whether this spells doom and gloom for cell replacement, the answer is absolutely not,\" said Kordower, who is pursuing another treatment for Parkinson's by using gene therapy to repair the damaged cells.

Isacson found no such damage in the brains of five patients who died nine to 14 years after getting transplants.

He said transplanting purified brain cells may provide better results. Isacson, who examined brain tissue from the patient studied by Kordower's team, said whole chunks of brain tissue had been transplanted into her -- including cells that could have provoked damaging inflammation.

\"I think that the transplant is basically triggering an immune reaction,\" Isacson said in a telephone interview.

Isacson wants to continue to try to treat Parkinson's patients with brain cell transplants, perhaps using stem cells that have been trained to grow into the specific brain cells affected in Parkinson's.

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帕金森氏病移植脑细胞能成活10年或以上， 三个研究团队在星期天报道，但至少部分移植细胞遭到破坏。这些损伤是否提示帕金森氏病是长期，持续进展的过程，持续的攻击脑细胞，或是因为移植本身。研究者的意见并不一致。但是他们都认同他们在自然研究杂志上发表的研究，提示时有争议的脑细胞移植对患者是有好处的。其中一个研究组成员，来自马萨诸塞州哈佛医学院和McLean医院的Ole Isacson医生说。“我们认为这些发现能使我们未来的研究更加乐观”。帕金森氏病在美国每年有超过100万患者，主要是因为产生多巴胺的脑细胞退化所致。药物能延缓症状一段时间，但没有很好的治疗方法，不能治愈。患者主要症状是抖动，进行性震颤加重，有时痴呆和死亡。一些团队用一些来源于流产胎儿的脑细胞进行移植治疗，以替代被疾病破坏的细胞。芝加哥的Rush 大学医学中心的Jeffrey Kordowerr 和同事，描述了一个61岁的女性病人，在接受移植后14年死亡。她的情况在开始时曾一度有所好转，但随即恶化直到死亡。脑细胞的的情况与帕金森氏病相似。Kordower研究组报道。他们写道：“这个病例说明移植到患者后，胎儿神经元也出现类似于帕金森氏病的典型的病理改变。”

持续进展过程

位于瑞典，Lund, Wallenberg神经科学研究中心的Patrik Brundin 和同事发现在移植到患者的一些细胞有一些损伤。但他们说，这些移植细胞存活了16年之久，并且有病人报道减轻了他们的症状。Kordower相信这些发现提示帕金森氏病在发病的数年中是一个持续进展的过程，在一个电话采访中说：“无话用什么药物，这个过程在帕金森氏病脑子中始终存在。”
他说只有5%的细胞受到损伤。“假如你问我是否这个细胞替代治疗是没有前景的，是注定要失败的，我的回答是：决不是。” Kordower说，他下一步正在细胞移植的基础上，为帕金森氏病寻找另一种治疗方法，用基因治疗修复损坏的脑细胞。

Isacson在5个病人的脑中并没有发现这种损伤，他们分别在移植后的9到14年死亡。
他说用纯化的脑细胞移植可能会产生更好的效果。 Isacson检查了Kordower小组病人的脑组织，他说，他们用大块脑组织进行了移植，包括能产生损伤性炎症反应的细胞。“我认为是移植触发了炎症反应。” Isacson在电话访谈中说。Isacson希望继续用脑细胞移植治疗帕金森氏病患者，也许可用能诱导向在帕金森氏病受到损伤的特殊脑细胞分化的干细胞进行移植。