CSNK2B gene replacement rescues autism-related phenotypes and establishes translational EEG biomarkers.

CSNK2B gene replacement rescues autism-related phenotypes and establishes translational EEG biomarkers.

Publication date: May 26, 2026

Variants in CSNK2B cause neurodevelopmental disorders with autism and epilepsy, but therapeutic evidence and translatable biomarkers remain limited. We generate Csnk2b haploinsufficient mice that recapitulate key disease features, including social and cognitive deficits, anxiety-like behavior, spontaneous seizures, cortical abnormalities, and reduced inhibitory interneurons. Early postnatal, brain-wide gene replacement improves survival and rescues structural, behavioral, and seizure phenotypes. Treatment also normalizes brain activity signatures linked to circuit function, including theta and gamma power, power ratios, interregional coherence, and gamma-band directional connectivity. These findings show that reduced Csnk2b dosage disrupts cortical development and network synchronization but can be corrected after birth. They also identify a compact set of noninvasive brain activity biomarkers with potential value for target engagement, dose selection, and longitudinal monitoring in future gene therapy studies.

Concepts Keywords
Autism autism
Biomarkers CSNK2B mutations
Haploinsufficient Csnk2b(+/−) mice
Neurodevelopmental epilepsy
Postnatal gene therapy

Semantics

Type Source Name
disease MESH autism
disease MESH neurodevelopmental disorders
disease MESH epilepsy
disease MESH anxiety
disease MESH seizures
drug DRUGBANK Albendazole

Original Article

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