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Dopamine-making neurons can be chemically controlled in animal model of Parkinson's

Thursday April 28, 2016

Bradley J. Fikes

The San Diego Union-Tribune - Stem cell-derived neurons transplanted into the brains of Parkinsons' patients may be controllable by drugs after transplantation, according to research performed in a mouse model of the disease.

If the work can be translated to humans, it would allow doctors to fine-tune the transplanted neurons to the needs of individual Parkinson's patients. However, it will take years before such a therapy can be tested in patients.

The mice received human dopamine-producing neurons. These are progressively destroyed in Parkinson's disease, impairing movement. The replacement neurons, grown from pluripotent stem cells, were genetically engineered to alter dopamine production in response to a drug.

The study was published Thursday in the journal Cell Stem Cell. The first author is Yuejun Chen, the senior author is Su-Chun Zhang; both of University of Wisconsin-Madison. When published online, the study can be found at: http://j.mp/parkneurons.

photoDopamine-making neurons can be chemically activated or inhibited, according to research on a possible new Parkinson's therapy. — University of Wisconsin/Madison

Transplants of fetal brain cells into Parkinson's patients illustrate why it's desirable to control these neurons after the operation, the study said. The results have been unpredictable: some patients have recovered the ability to move normally, while others experienced involuntary movements characteristic of an "overdose" of the cells.

Researchers are trying to improve these results by making neurons from stem cells, a source that can be subjected to precise quality control. Carlsbad-based International Stem Cell Corp. recently began a clinical trial of its approach, which grows the neurons from cells produced from parthenogenetic, or unfertilized human egg cells.

And a San Diego-based group called Summit for Stem Cell has grown dopamine-producing neurons from artificial embryonic stem cells called induced pluripotent stem cells. These cells are derived from the patients to be treated. The group has held preliminary talks with federal regulators. Before it can more forward, the group needs to raise millions to conduct the clinical trial.

The study is sound, said Andres Bratt-Leal, Senior Scientist for Summit For Stem Cell, and the technology might eventually incorporated into the approach taken by the group. But first, Summit For Stem Cell must successfully test the transplant protocol it has already devised, Bratt-Leal said. Then the group can incorporate refinements.

"It's a really neat trick that they did, and it's a really great research tool," Bratt-Leal said. "In terms of how it relates to our project, it's not something we would do the first go-around. It's something I could see groups using in version 2.0, after you have a cell therapy that you know that works."

Version 1.0 will provide needed information to design the drug-controllable neurons, Bratt-Leal said. For example, it would be helpful to know the variation in individual response to the transplanted neurons.

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http://www.sandiegouniontribune.com/news/2016/apr/28/parkinsons-stem-cell-control/