Thursday, May 9, 2013

Transplanted neurons treat mice with epilepsy

Transplanted neurons treat mice with epilepsy. Courtesy of Scott Baraban, Robert Hunt, and Kelly Girksis
Our grantees at UCSF overachieved this week, showing both that transplants of a certain cell type can treat epilepsy in mice, and that they can generate those cells starting with human stem cells -- either embryonic or reprogrammed.

First, the epileptic mice. That work was published May 5 in Nature Neuroscience. The researchers isolated a type of cell from the brains of mice called a medial ganglionic eminence (MGE) cells. Not to worry, we'll just call them MGEs from here. These are early stage cells that go on to form a cell type that's lost in parts of the brain where epileptic seizures occur, and are also known to help calm other neurons. So, they seemed promising.

The group then transplanted these cells into the brains of mice with epilepsy. Jeffrey Norris of UCSF described their findings like this:
In the UCSF study, the transplanted inhibitory cells quenched this synchronous, nerve-signaling firestorm, eliminating seizures in half of the treated mice and dramatically reducing the number of spontaneous seizures in the rest. Robert Hunt, PhD, a postdoctoral fellow in the Baraban lab, guided many of the key experiments.
Norris then quotes Scott Baraban, who led the study:
“These cells migrate widely and integrate into the adult brain as new inhibitory neurons,” Baraban said. “This is the first report in a mouse model of adult epilepsy in which mice that already were having seizures stopped having seizures after treatment.”
You might have noticed that all this good news is in mice. Well, some of the same authors on this study also published a paper in the May 2 issue of Cell Stem Cell showing that they could create these MGE cells starting with human stem cells rather than mouse. And, those human-derived cells also integrated into mouse brains and seemed to form normal connections. That's one sign that the cells might be able to do the same if transplanted into people.

One interesting point is that MGE cells also seem to play a role in managing pain, and in Parkinson's disease. Norris quotes Arnold Kriegstein, who was co-lead author on this work:
“We think this one type of cell may be useful in treating several types of neurodevelopmental and neurodegenerative disorders in a targeted way.”
The group says they are hoping to someday test the cells in people. That process, which involves verifying that the cells really do work, testing them in much larger numbers of animals and making sure they don't cause worrisome side effects, generally takes at least five years.

CIRM funding: Arturo Alvarez-Buylla (TR2-01749), Arnold Kriegstein (RC1-00346), John Rubenstein (RB2-01602)

A.A.

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