Drug Reverses Abnormal Brain Function in Rett Syndrome Mice

A promising study out today in the prestigious Journal of Neuroscience showed that in a mouse model of Rett syndrome, researchers were able to reverse abnormalities in brain activity and improve neurological function by treating the animals with an FDA-approved anesthesia drug, ketamine. Rett syndrome is among the most severe autism-related disorders, affecting about one in 10,000 female births per year, with no effective treatments available.

“These studies provide new evidence that drug treatment can reverse abnormalities in brain function in Rett syndrome mice,” says David Katz, PhD, professor of neurosciences, Case Western Reserve University School of Medicine and senior author of the study. “They also provide new leads as to what kinds of drugs might be effective in individuals with Rett syndrome.”

Neuroscientists at Case Western Reserve University School of Medicine were able to successfully map differences in the brain activity of normal mice and those with a genetic mutation that mirrors the cause of Rett syndrome in humans. They found that – compared to normal mice – Rett syndrome mice showed regions of abnormally low activity in the front of the brain (forebrain) and regions of abnormally high activity in the back of the brain (brainstem). Importantly, they found that the regions of low activity overlap with regions of the brain that are also under-active in humans with classic autism. This indicates there may be common mechanisms underlying abnormal behaviors in the two diseases.

The identification of these brain regions provided clues into specific areas to target for treatment. Based on previously published findings that ketamine activated neurons in the forebrain, the researchers gave the drug to the Rett syndrome mice and found it increased levels of brain activity in those regions and improved neurological function. Importantly, the drug was effective at a low dose that did not produce anesthesia.