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Researchers have used stem cells obtained from human embryos to successfully treat Parkinson's disease in mice and rats, a key step in the quest to develop a similar approach for people.
In a study published Sunday in the journal Nature, scientists described how they converted human embryonic stem cells into nerve cells that produced the brain chemical dopamine. When these nerve cells were transplanted into the brains of mice and rats, they released dopamine and got rid of the animals' Parkinson's symptoms. The cells were also successfully transplanted into rhesus monkeys, whose biology is closer to that of humans.
"We see a real opportunity to develop this into an actual cell therapy for patients," said Lorenz Studer, lead author of the paper and a stem-cell biologist at Sloan-Kettering Institute for Cancer Research in New York. "It is now more of an engineering problem" than a scientific one.
Nerve cells use dopamine to help control muscle movement. In Parkinson's disease, for which there is no cure, the brain's dopamine-producing cells slowly get destroyed. This affects the brain's ability to send messages, leading to loss of muscle function, reduced movement and tremors. There are drugs that increase dopamine in the brain and help control symptoms, but they can cause side effects, such as involuntary movements. Their benefits also tend to wax and wane as the disease progresses.
Some scientists are experimenting with cell-transplantation. They have used stem cells from mouse embryos to make dopamine-producing cells and treat Parkinson's in animals. But until now, a similar approach in mice using human embryonic cells hasn't worked well. Not only have human-derived dopamine cells not perform efficiently when transplanted into animals, they have also triggered the growth of unwanted tumor-like structures.
In those past experiments, scientists typically added two specialized proteins, known as growth factors, that turned embryonic stem cells into dopamine-producing nerve cells. Now, by adding a third substance, Dr. Studer and his colleagues were able to activate a vital biological pathway in the embryonic cells, thus making human dopamine cells that worked much better. Crucially, their approach didn't lead to tumor-like structures.
The researchers first experimented with mice that had no dopamine cells—after scientists' intervention—and thus suffered from Parkinson's disease on one side of their brain. When given an amphetamine, the stimulated mouse would move. But because only one side of its brain had dopamine cells, it triggered a much stronger movement on that side than on the other. That caused the animals to spin around up to 15 times a minute.
About 100,000 human-derived dopamine cells were then injected into the side of the mouse brain that lacked dopamine cells. Over a period of three to five months, as the transplanted dopamine cells took hold, the animals regained movement in that part of the brain.
Their rotational movements gradually declined, then stopped altogether. Similar results were seen in rats.
"This is a big leap" in the effort to use cell-transplantation to one day treat Parkinson's patients, said Tilo Kunath, a stem-cell scientist at the University of Edinburgh, who read the study but wasn't involved in it. "To see a complete rescue, and a lasting rescue, is unheard of in these animal models."