One-time cell transplantation cures epilepsy in mice
Earlier this week we reported on a neurological implant that has been found to accurately predict the onset of epileptic seizures. But a discovery by researchers at the University of California, San Francisco (UCSF) could one day render such a device obsolete. By transplanting a specific type of cell into the brain, the researchers have been able to cure epilepsy in adult mice, with hopes a similar treatment could work in humans.
Epileptic seizures are caused by the abnormal firing of many excitatory nerve cells in the brain at the same time, resulting on extreme muscle contractions. The UCSF scientists were able to inhibit this nerve-signaling firestorm and eliminate seizures in half the treated mice and dramatically reduce the number of spontaneous seizures in the rest with a one-time transplantation of medial ganglionic eminence (MGE) cells into the hippocampus, a region of the brain associated with learning and memory, as well as seizures. The mice also became less abnormally agitated, less hyperactive, and performed better in water-maze tests.
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MGE cells are progenitor cells that form early in the embryo and inhibit signaling in overactive nerve circuits by generating mature inhibitory nerve cells called interneurons. The researchers found that the transplanted MGE cells from mouse embryos migrated and generated interneurons that integrated into existing neural circuits, essentially replacing the cells that fail in epilepsy.
“Our results are an encouraging step toward using inhibitory neurons for cell transplantation in adults with severe forms of epilepsy,” said Scott C. Baraban, PhD, who holds the William K. Bowes Jr. Endowed Chair in Neuroscience Research at UCSF and led the new study. “This procedure offers the possibility of controlling seizures and rescuing cognitive deficits in these patients.”
In related research that gives hope for human patients, Baraban’s team also found a way to reliably generate human MGE-like cells in the laboratory. When these cells were transplanted into healthy mice, they also generated functional inhibitory nerve cells.
The team used a mouse model of disease that is meant to resemble a severe and typically drug-resistant form of human epilepsy called medial temporal lobe epilepsy, which often develops in adolescence and in which seizures are thought to arise in the hippocampus. The research seemed to bear this out, with transplantation of the MGE cells in to the amygdala failing to halt seizure activity in the same mouse model.
The team’s findings appear in the journal Nature Neuroscience.