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12th May 2013

Epilepsy cured in mice

Epilepsy is among the most common of the serious neurological disorders, affecting some 50 million people around the world. A new brain cell therapy raises hope for severe forms of the disease.

 

epilepsy

 

Epilepsy that does not respond to drugs can be halted in adult mice by transplanting a specific type of cell into the brain, UC San Francisco researchers have discovered, raising hope that a similar treatment might work in humans.

The scientists controlled seizures in epileptic mice with a one-time transplant of medial ganglionic eminence (MGE) cells, which inhibit signalling in overactive nerve circuits, into the hippocampus – a brain region associated with seizures, as well as with learning and memory. Other researchers had previously used different cell types in rodent cell transplantation experiments and failed to stop seizures.

Cell therapy has become an active focus of epilepsy research, in part because current medications, even when effective, only control symptoms and not the underlying causes of the disease, according to Scott Baraban, who led the new study. In many types of epilepsy, he said, current drugs have no therapeutic value at all.

"Our results are an encouraging step toward using inhibitory neurons for cell transplantation in adults with severe forms of epilepsy. This procedure offers the possibility of controlling seizures and rescuing cognitive deficits in these patients."

The findings, which are the first ever to report stopping seizures in mouse models of adult human epilepsy, were published online this week in Nature Neuroscience.

During epileptic seizures, extreme muscle contractions and often a loss of consciousness can cause seizure sufferers to lose control, fall and sometimes be seriously injured. The unseen malfunction behind these effects is the abnormal firing of many excitatory nerve cells in the brain at the same time.

In the UCSF study, the transplanted inhibitory cells quenched this synchronous, nerve-signalling firestorm, eliminating seizures in half of the mice and dramatically reducing the number of spontaneous seizures in the rest. The MGE cells migrated and generated interneurons, in effect replacing the cells that fail in epilepsy. The treated mice – in addition to having fewer seizures – became less abnormally agitated, less hyperactive and performed better in water-maze tests.

In another encouraging step, a separate study from the same university found a way to reliably generate human MGE-like cells in the laboratory. When transplanted into mice, these cells similarly inhibited the overactive nerves.

 

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