Explaining the Link Between Autism and Epilepsy
One third of children who have autism spectrum disorder also have epilepsy, but until recently, scientists haven’t been able to explain why. They knew the epilepsy was related to a major autism-risk gene — but the connection wasn’t clear between children’s seizures and the mutated gene behind some autism cases.
Now, scientists at Northwestern University in the US have discovered the link: the mutation acts like a bad gardener in the brain. Neurons are connected through tiny branches and leaves (more technically, through dendrite arbors and synapses) that enable the brain cells to relay vital messages and control activity. The mutated gene associated with a risk for autism also causes these branches and leaves to shrink, causing a breakdown in message delivery. One important message that gets lost? Calm Down! And what happens when it gets lost? Seizures.
The ‘calm down’ message comes from a type of brain cell called inhibitory neurons, whose job it is to keep the brain functioning tranquilly and slam the brake on excitatory neurons. In kids with the autism-risk mutation, inhibitory neurons don’t grow enough branches and leaves to communicate their soothing message, the scientists found. Which means excitatory neurons continue firing — which leads to epilepsy.
“Now we can start testing drugs to treat the seizures as well as other problems in autism,” said Peter Penzes, of Northwestern University’s Feinberg School of Medicine and director of its new Center for Autism and Neurodevelopment. Penzes is the lead author of the study published in Molecular Psychiatry. “Patients with the mutation also have language delay and intellectual disability. So a drug targeting the mutation could have multiple benefits.”
The mutation, CNTNAP2 or better known as “catnap2,” works as a team with another mutated gene, CASK, implicated in impaired cognitive development. As a result, scientists have a new target for drugs to treat the disorder. While catnap2 is a difficult molecule to target with drugs, Penzes said, its partner, CASK, interacts with many other molecules, making it more easily inhibited or activated with drugs. In fact, when scientists blocked CASK in the study, dendrites didn’t grow. Next, Penzes team will see if the reverse is possible — whether targeting CASK will enable neural connections to grow and the ‘calm down’ message to get through.