Autism exists on a broad spectrum, from individuals with profound support needs to those with extraordinary abilities, shaping social experience in deeply individual ways. This heterogeneity has historically made it challenging to identify clear genetic markers for autism spectrum disorder (ASD). However, for a subset of individuals, mutations in the SCN2A gene represent a monogenic form of autism: one driven by a single gene.SCN2A encodes the Nav1.2 sodium channel protein, which is essential for proper neuronal signalling and communication in the brain. Mutations in SCN2A can lead to debilitating seizures, movement disorders like dystonia, intellectual disability, and in cases without early-onset seizures, profound autism. Loss-of-function mutations in SCN2A can lead to haploinsufficiency, meaning only one functional copy of the gene remains, producing roughly half the normal amount of protein and leads to profound autism and represents a monogenetic form of the condition.
Scientists have developed mouse models that mimic this haploinsufficiency, exhibiting similar neurological and behavioral challenges. In a groundbreaking study published in Nature in September 2025, researchers Kevin Bender and Nadav Ahituv at the University of California, San Francisco (UCSF), used CRISPR activation (CRISPRa), a targeted gene upregulation technology, to boost expression from the remaining functional SCN2A allele. In these mouse models, the approach restored Nav1.2 protein levels to near-normal, rescued neuronal excitability and synaptic maturation, normalized brain signalling, and protected against seizures, even when treatment was initiated in adolescent mice (equivalent to school-age children in humans). Importantly, the therapy showed promise in human stem cell-derived neurons carrying SCN2A haploinsufficiency, highlighting its potential translation to patients. This mutation-agnostic strategy offers real hope for individuals and families affected by SCN2A-related disorders, including those with autism and intellectual disability. It also opens doors to deeper insights into the molecular mechanisms underlying autistic phenotypes and related neurodevelopmental conditions.
February 24th is International SCN2A Awareness Day, a time to shine a light on this rare genetic condition and celebrate progress in research (www.scn2a.org). At NeuroNetworks Fund, we stand with the SCN2A community, advocating for accelerated development of therapies for serious neurological disorders like autism and epilepsy. We are inspired by innovations like this UCSF breakthrough and committed to bridging the gap between promising science and real-world treatments. Together, let’s raise awareness and fuel hope for a brighter future.
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