Researchers from the Hector Institute for Translational Brain Research in Germany have explored how the drug lamotrigine, commonly used to treat epilepsy and bipolar disorder, might influence the progression of autism. The findings, published in Molecular Psychiatry, add new observations about how this medication can modulate brain activity patterns associated with the condition. The study suggests that lamotrigine’s impact on neuronal signaling could help temper some of the electrical imbalances seen in autistic brains, offering a potential avenue for therapeutic exploration beyond its traditional indications.
Autism presents with a range of behavioral traits linked to numerous genetic changes. In the latest work, scientists identify a molecular mechanism involving the MYT1L protein, which normally regulates the expression of several genes in nerve cells. When MYT1L activity is disrupted, it may contribute to neural circuit changes observed in autism. Mutations affecting the MYT1L gene have already been connected with a spectrum of neurological conditions, including schizophrenia, epilepsy, and certain brain malformations, underscoring the broader importance of this regulatory protein in brain development and function.
To probe this pathway, researchers reduced MYT1L activity in human neurons derived from stem cells. The cells displayed heightened electrical excitability, a feature linked to autistic phenotypes, driven in part by increased production of sodium channels that permit sodium ions to flow into the neuron. This sodium influx is essential for signaling in nerve cells, yet excessive entry can push neural networks toward overactivity. By applying lamotrigine, the scientists were able to dampen these altered sodium channels, which helped restore a more balanced electrical profile in the cultured neurons.
In parallel experiments, the team created mice engineered to lack the MYT1L protein. These animals showed brain structure differences and several behaviors reminiscent of autism. Remarkably, when treated with lamotrigine, many of these abnormalities were less pronounced, suggesting the drug’s potential to counter some neural disturbances tied to MYT1L dysfunction in this model. The observed improvements point to a mechanism where reducing excitability in neural circuits may translate into behavioral stabilization in this specific context.
Looking ahead, scientists are cautious about extrapolating these results to humans. While the data from cell cultures and animal models are promising, translating such findings into effective adult therapies for autism requires careful, well-designed clinical investigations. Current plans are moving forward with early-stage trials to evaluate lamotrigine’s safety and potential efficacy in a broader group of individuals with autism spectrum traits. The work emphasizes a broader strategy: targeting the imbalance between excitation and inhibition in brain circuits as a route to improving function and quality of life for some people affected by autism.