Anti-tau treatment blocks a form of pediatric epilepsy

A reduction in tau protein levels in the brain effectively curtails the progression of Dravet syndrome, a serious form of epilepsy in children, the Gladstone Institutes announced Aug. 13.

Scientists at the Gladstone Institutes, based in San Francisco, have conducted a preclinical study to evaluate the benefit of reducing tau levels in the brain in a mouse model of Dravet syndrome. Researchers found that not only did reducing tau suppress seizures and improved survival, but it also led to better cognitive function. This is the first study of its kind looking into anti-tau therapy for intractable genetic epilepsy.

"It would really be wonderful if tau reduction turned out to be useful not only in Alzheimer's disease, but also in other disabling neurological conditions for which there currently are no effective treatments," said senior author Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease and a professor of neurology and neuroscience at the University of California, San Francisco, in a press release. "We suspected that this approach might be beneficial in Dravet, but we couldn't be sure because of the severity of this syndrome and the corresponding model. We are thrilled that our strategy was so effective, but a lot more work is needed to advance it into the clinic."

Current treatments have not been shown to be effective. Dravet develops from a genetic variant affecting the brain’s sodium channels. The disease typically involves intense and repeated seizures and a 20 percent chance of death from the disease and often complicated cognitive and behavior problems for those who survive.

"I am especially excited about the improvements we observed in cognitive and behavioral dysfunctions because these abnormalities are particularly hard on the kids--and their parents," said co-author of the study Ania Gheyara, MD, PhD, a staff scientist at Gladstone also with the UCSF Department of Pathology. "Our hope is that this approach will be broadly applicable to many different types of epilepsy."

By deleting one copy of the affected gene, researchers saw significant relief from most symptoms and taking out both copies almost wiped out all signs of disease and normalization of brain activity. Anti-tau therapy also improved behavior, memory and learning in mouse models. Details of the study were published in Annals of Neurology.

The researchers will next develop a therapy for humans in further preclinical trials, which Gladstone is “pursuing actively," said Mucke.