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The tau protein found in the brain has been mainly linked to the development of the most common form of dementia, Alzheimer's disease. In a new study, researchers set out to see how levels of tau can affect another neurological illness, Dravet syndrome, which is a severe intractable form of childhood epilepsy. The team discovered that reductions in tau led to the suppression of seizure activity and a reduction in the premature death risk. These lower levels were also tied to improving the cognitive and behavioral abnormalities associated with the disease.

"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, the director of the Gladstone Institute of Neurological Disease and a professor of Neurology and Neuroscience at the University of California, San Francisco. "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."

The researchers from Gladstone Institute had previously studied tau levels in relation to Alzheimer's and wanted to switch the focus onto Dravet syndrome, which is caused by a genetic mutation that impacts the sodium channels in the brain. Symptoms include seizures, cognitive impairment and behavioral problems that are similar to autism. Patients with this syndrome have an up to 20 percent risk of dying prematurely.

In the study, the team genetically created mouse models with Dravet syndrome and reduced their levels of tau protein by suppressing the activity of the gene responsible for producing the protein. The researchers noted that by deleting one copy of the gene, the rodents' symptoms improved dramatically. When they deleted two copies of the gene, they found that the symptoms were almost all eliminated.

"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 first author Ania Gheyara, MD, PhD, a staff scientist at Gladstone who is also affiliated with the UCSF Department of Pathology, reported in the press release. "Our hope is that this approach will be broadly applicable to many different types of epilepsy."

The study, "Tau reduction prevents disease in a mouse model of Dravet syndrome," was published in the Annals of Neurology.