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Brain Cell Transplants Are Being Tested Once Again For Parkinson's

Tuesday June 13, 2017

When the neurons that release the neurotransmitter dopamine die, people develop Parkinson's disease.
John Hamilton

© 2017 npr -

Researchers are working to revive a radical treatment for Parkinson's disease.

The treatment involves transplanting healthy brain cells to replace cells killed off by the disease. It's an approach that was tried decades ago and then set aside after disappointing results.

Now, groups in Europe, the U.S. and Asia are preparing to try again, using cells they believe are safer and more effective.

"There have been massive advances," says Claire Henchcliffe, a neurologist at Weill Cornell Medicine in New York. "I'm optimistic."

"We are very optimistic about ability of [the new] cells to improve patients' symptoms," says Viviane Tabar, a neurosurgeon and stem cell biologist at Memorial Sloan Kettering Cancer Center in New York.

Henchcliffe and Tabar joined several other prominent scientists to describe plans to revive brain cell transplants during a session Tuesday at the International Society for Stem Cell Research meeting in Boston.

Their upbeat message marks a dramatic turnaround for the approach.

During the 1980s and 1990s, researchers used cells taken directly from the brains of aborted fetuses to treat hundreds of Parkinson's patients. The goal was to halt the disease.

Parkinson's destroys brain cells that make a substance called dopamine. Without enough dopamine, nerve cells can't communicate with muscles, and people can develop tremors, have difficulty walking and other symptoms.

Drugs can temporarily raise dopamine levels, easing symptoms. But their effectiveness tends to wane over time.

So researchers thought a better approach would be to simply replace the cells that produce dopamine. "The rationale is that if those cells are lost, and we know they make dopamine, and we know that dopamine is important for good coordination, good automatic movement, why could we not replace those cells," Henchcliffe says.

For some patients, the transplanted fetal cells produced dramatic improvements. But rigorous studies eventually showed that many other patients were not helped. And some developed an unwelcome side effect: uncontrolled movements.

So in 2003, researchers declared a moratorium on transplants for Parkinson's. "There was a stepping back to re-evaluate what exactly just happened," Henchcliffe says.

That took a while. But it's clear now that over the long term, some patients really were helped by the procedure.

Henchliffe got to examine five people who'd received transplants more than 15 years earlier.

"These were patients with decades of Parkinson's disease, and I thought it was really striking that a subset actually seemed to be doing much better than one would expect," she says.

Meanwhile, researchers never stopped looking for ways to make cell transplants safer and more effective.

The early transplants were pretty crude, Tabar says. One problem was that the cells came directly from the brains of fetuses, she says.

"What you were placing in the patient was just a soup of brain," she says. "It did not have only the dopamine neurons, which exist in the tissue, but also several different types of cells."

Some of those other cells may also have grown in the patients' brains, causing side effects, she says.

To prevent that sort of problem, scientists at Sloan Kettering have spent the past dozen years figuring out how to turn stem cells into pure lines of dopamine cells in the lab.

Unlike the transplanted fetal cells, these cells are an exact replacement for the neurons that produce dopamine in an adult brain, "So you are confident that everything you are putting in the patient's brain will consist of right type of cell," Tabar says.

Another advantage of lab-grown cells is that the supply is unlimited. "Not only can we grow them, in fact we have almost 1,000 doses of these cells already sitting in a freezer," Tabar says.

Tabar, along with her colleague and husband, Lorenz Studer, hope the Food and Drug Administration will give them permission to begin testing those cells in Parkinson's patients in 2018.

Both have a financial stake in a startup that's funding the project.

Meanwhile, several other groups around the globe are also launching transplant studies. Researchers say a handful of patients in Australia have already received cells.

Some scientists are worried that the renewed rush to make transplants work could lead to more disappointments.

But Tabar says the time is right. "On the one hand, you don't want to rush," she says. "On the other hand I think the field is ready for something bold."

http://www.npr.org/sections/health-shots/2017/06/13/532792500/brain-cell-transplants-are-being-tested-once-again-for-parkinsons

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