Genetic mutations and neurodevelopmental disorders: the study that reveals new treatment possibilities

The field of neuroscience continues to advance thanks to research that allows for a better understanding of the causes and potential treatments of complex neurodevelopmental disorders. A recent study conducted by a team of CONICET scientists at the Institute for Biochemical Research of Bahía Blanca (INIBIBB) uncovered a link between mutations in the PTEN gene and alterations in neuronal development. This finding opens the door to new therapeutic possibilities based on simple metabolic interventions, such as ketogenic diets, which could improve the well-being of individuals with disorders such as autism.

The PTEN gene and its role in neurodevelopment

The study, published in eLife, investigated the effects of mutations in the PTEN gene, which is associated with various neurodevelopmental disorders, including autism spectrum disorders (ASD). PTEN encodes a protein that regulates fundamental cellular functions, and when altered, can lead to nervous system dysfunctions.

The researchers focused on the worm Caenorhabditis elegans (C. elegans), an experimental model widely used in biology to study molecular processes common to many organisms, including vertebrates.

The study revealed that mutations in the PTEN homolog gene, called DAF-18, significantly disrupted the balance between neuronal excitation and inhibition. In particular, GABAergic inhibitory neurons—critical for regulating the nervous system—showed functional deficiencies. These neurons are responsible for maintaining the proper balance between excitatory and inhibitory signals in the brain, which is essential for healthy neuronal development.

Potential treatments through the ketogenic diet

A key aspect of the study was that exposing mutant worms to β-hydroxybutyrate, a metabolite produced during ketosis (induced by ketogenic diets), improved the structural and functional defects of GABAergic neurons. This suggests that relatively simple metabolic interventions, such as ketogenic diets, could provide therapeutic benefits for disorders associated with PTEN gene mutations.

The ketogenic diet, characterized by low carbohydrate intake and high fat and protein content, has already proven effective in treating several neurological conditions, including certain neurodevelopmental disorders. The findings of this study provide a new perspective on how diet-generated metabolites can help reduce neuronal defects and restore the balance between brain excitation and inhibition.

Although the study was conducted in C. elegans and cannot be directly extrapolated to humans, it establishes a solid foundation for future research aimed at developing therapies to restore neural balance through metabolic or dietary modifications. Moreover, these results may apply not only to PTEN-associated disorders but also to other neurodevelopmental conditions involving inhibitory neuron dysfunction.

Advances in understanding neurodevelopmental disorders and new research directions

This study represents a significant step forward in understanding how PTEN mutations affect neurodevelopment and how some defects can be corrected through simple metabolic interventions. According to Diego Rayes, CONICET researcher and one of the study coordinators, the findings open new opportunities to treat complex disorders with strategies that are accessible and relatively easy to implement.

The identification of β-hydroxybutyrate as a potential treatment offers an interesting pathway for developing therapies that may benefit individuals with ASD and other neurodevelopmental conditions.

It is important to emphasize, however, that further research—particularly in mammals—is necessary to evaluate the clinical relevance of these findings. As studies progress, researchers will be able to explore how other genetic mutations and non-genetic factors influence neurodevelopment and how they may be addressed through personalized metabolic or dietary interventions.

These results undoubtedly mark the beginning of new research avenues with the potential to positively impact the lives of many people.