The CNTNAP2 gene is known to be mutated in autism with epilepsy. The current study proposes a mechanism that may link the two conditions.
"Our model is that the CNTNAP2 ectodomain (the part of the protein that extends into the extracellular space) is part of a natural mechanism through which the brain protects itself from too much activity, or seizures," Dr. Peter Penzes of Northwestern University Feinberg School of Medicine, Chicago, told Reuters Health by email. "When brain cells are too active for some reason, they produce more CNTNAP2 ectodomain, which floats away and binds to other brain cells, to quiet them down."
"In patients with mutations in CNTNAP2, such as a famous extended family of Amish people, or Pitt Hopkins-like syndrome 1, or even autism in general, this mechanism does not work, so their brains are more prone to epilepsy," he explained.
The CNTNAP2 ectodomain "also leaks into the cerebrospinal fluid (CSF), where we can measure it, so it can give us a clue for how much is produced in the brain," he said.
These insights came from the current study, published in Neuron, in which Dr. Penzes and colleagues first analyzed CSF from individuals with autism and epilepsy. Detecting a portion of cntnap2 in the CSF was "unexpected," Dr. Penzes noted. Levels of the CNTNAP2 ectodomain "were much lower in autism patients than in healthy controls."
Delving more deeply in mouse models, the team discovered that the brain produced more CNTNAP2 ectodomain when mice were undergoing seizures as a way of reducing this overactivity. "It quieted them down, acting like an antiepileptic," he said. In that sense, "Cntnap2 is the first 'endogenous antiepileptic.'"
These investigations point to "two important conclusions," he said. Finding that the brain produces molecules to help it avoid seizures and that when these molecules are at low levels, epilepsy is more likely to occur, is a mechanism that could lead to a new class of antiepileptic drugs within the next five to 10 years, he predicted.
Identification of autism biomarkers in CSF could happen within one-to-two years, he said. "Cntnap2 could be one, but our study needs replication in many more patients."
SOURCE: https://bit.ly/3EzJYnP Neuron, online December 17, 2021.
By Marilynn Larkin
Posted on
site created by:
© 2021 Medicom Medical Publishers. All rights reserved. Terms and Conditions | Privacy Policy