Optical fibers implanted in the brain can activate light-sensitive proteins that stop epileptic seizures as they are detected. The technique, developed at the University of California, Irvine, could help the more than 3 million Americans who suffer from epilepsy, a recurrent spontaneous seizure condition. “In the US alone, nearly 500 new cases of epilepsy are diagnosed every day,” postdoctoral scholar Esther Krook-Magnuson told BioPhotonics. “There needs to be more and better treatment options for epilepsy than those currently available.” Current drug therapy is ineffective in more than 40 percent of patients, she said. The on-demand optogenetic method, developed in the lab of Ivan Soltesz, targets specific cell populations in the hippocampus – a critical brain region in temporal lobe epilepsy – to stop seizures in a mouse model using an electroencephalograph (EEG)-based computer system. Ivan Soltesz, UC Irvine Chancellor’s Professor and chair of anatomy and neurobiology, has helped shed light on the inner working of the human brain. His research offers hope to millions suffering from epilepsy. Courtesy of Steve Zylius/University Communications. “The system is designed to detect, in real time, seizures during the early phase … before there is any large, overt behavior,” Krook-Magnuson said. “Once a seizure is detected, intervention (light delivery) is triggered. The software examines various features of the EEG, and the experimenter can tune the detector to the specific features of the seizures in individual animals.” If such seizures begin with several, regular-spaced spikes, she said, the experimenter can set the parameters such that the program recognizes the “signature” at the start of a seizure. During testing, the size of the effect varied between approaches, seizure types and individual animals. “In one animal, every electrographic seizure stopped when the light was turned on,” she said. “Overall, we saw a 30 percent reduction in the number of behavioral seizures.” The hippocampus (background image) is a critical brain region in temporal lobe epilepsy. Esther Krook-Magnuson et al report that on-demand optogenetics targeting specific cell populations in the hippocampus stops seizures (EEG traces in image) in a mouse model of temporal lobe epilepsy, demonstrating the feasibility of a spatially, temporally and cell-type specific treatment for this devastating disorder. Courtesy of Caren Armstrong. The approach could be effective for treating a range of seizure types, including severe “tonic-clonic” events – the type of generalized seizure (formerly known as grand mal and most commonly associated with epilepsy) that affects the entire brain. Although the study has been carried out only in mice, the Soltesz lab is confident that the work could lead to a better alternative to the currently available electrical stimulation devices. “There are two main hurdles to overcome before this device could be used in humans,” Krook-Magnuson said. “First, there needs to be an implantable device which can do what we did in the mice, without a person having to be attached to a large computer.” Groups are now working on a wireless device to detect seizures and deliver light. The second is to get light-sensitive proteins called opsins to express in the correct brain cells. Achieving this will require tools used to deliver genetic material into cells called viral vectors, which are already being used in clinical trials to treat other diseases, she said. The study was published in Nature Communications (doi: 10.1038/ncomms2376).