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Reprogrammed cells relieve Parkinson's symptoms in monkeys

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Japanese researchers report promising results from an experimental therapy for Parkinson’s disease that involves implanting neurons made from reprogrammed stem cells into the brain. A trial conducted in monkeys with a version of the disease showed that the treatment improved their symptoms and seemed to be safe, according to a report published August 30 in Nature.

The study’s key finding — that the implanted cells survived in the brain for at least two years without causing any dangerous effects in the body — provides a major boost to researchers’ hopes of testing stem cell treatments for Parkinson’s in humans, say scientists. 

Jun Takahashi, M.D., Ph.D., a stem cell scientist at Kyoto University in Japan who led the study, said that his team plans to begin transplanting neurons made from induced pluripotent stem (iPS) cells into people with Parkinson’s in clinical trials soon.

The research is also likely to inform several other groups worldwide that are testing different approaches to treating Parkinson’s using stem cells, with trials also slated to begin soon.

Parkinson’s is a neurodegenerative condition caused by the death of cells called dopaminergic neurons, which make a neurotransmitter called dopamine in certain areas of the brain. Because dopamine-producing brain cells are involved in movement, people with the condition experience characteristic tremors and stiff muscles. Current treatments address symptoms of the disease but not the underlying cause.

Researchers have pursued the idea that pluripotent stem cells, which can form any cell type in the body, could replace dead dopamine-making neurons in people with Parkinson’s and thus potentially halt or even reverse disease progression. Embryonic stem cells, derived from human embryos, have this capacity, but they have been the subject of ethical debates. But iPS cells, which are made by coaxing adult cells into an embryonic-like state, have the same versatility without the associated ethical concerns.

What did the latest study find?

Dr. Takahashi’s team transformed iPS cells derived from both healthy people and those with Parkinson’s into dopamine-producing neurons. They then transplanted these cells into macaque monkeys with a form of the disease induced by a neuron-killing toxin.

The transplanted brain cells survived for at least two years and formed connections with the monkey’s brain cells, potentially explaining why the monkeys treated with cells began moving around their cages more frequently.

Why is the research important?

Crucially, Dr. Takahashi’s team found no sign that the transplanted cells had developed into tumors — a key concern with treatments that involve pluripotent cells — or that they evoked an immune response that couldn’t be controlled with immune-suppressing drugs.

“It’s addressing a set of critical issues that need to be investigated before one can, with confidence, move to using the cells in humans,” said Anders Bjorklund, M.D., Ph.D., a neuroscientist at Lund University in Sweden.

When will clinical trials begin and how will they work?

“I hope we can begin a clinical trial by the end of next year,” Dr. Takahashi said. Such a trial would be the first iPS cell trial for Parkinson's.

In theory, iPS cells could be tailor-made for individual patients, which would eliminate the need to use drugs that suppress a possible immune response to foreign tissues.

But customized iPS cells are expensive to make and can take a couple months to derive and grow, Dr. Takahashi noted. So instead his team plans to establish iPS cell lines from healthy people and then use immune cell biomarkers to match them to people with Parkinson’s in the hope of minimizing the immune response (and therefore the need for drugs to blunt the attack).

In a study described in an accompanying paper in Nature Communications, Dr. Takahashi’s team implanted into monkeys iPS-cell-derived neurons from different macaques. They found that transplants between monkeys carrying similar white blood cell markers triggered a muted immune reaction.

Learn more:

http://www.nature.com/news/reprogrammed-cells-relieve-parkinson-s-symptoms-in-trials-1.22531#/ref-link-1
http://dx.doi.org/10.1038/nature23664