Innovative Treatment Targets Neurobehavioral Symptoms in Neurofibromatosis Type 1

Recent research from Indiana University School of Medicine has unveiled a promising therapeutic approach for addressing the neurobehavioral challenges associated with neurofibromatosis type 1 (NF1), a genetic disorder affecting the nervous system and skin. Published in the Journal of Clinical Investigation, the study highlights strategies that could benefit not only NF1 patients but also thousands of individuals with related rare genetic conditions.

NF1 impacts approximately 1 in 3,000 individuals globally and is widely recognized for causing nerve tumors. However, a less visible yet critical aspect of the disease involves neurodevelopmental disorders, with 50 to 70% of children with NF1 diagnosed with autism spectrum disorder or ADHD. Currently, treatment options for these neurobehavioral issues are limited, mainly confined to conventional medications without targeted therapies for NF1-specific symptoms.

The disorder results from mutations in the NF1 gene, which encodes a protein called neurofibromin. Neurofibromin regulates cell growth and neural processes; mutations cause a reduction in its levels—a condition known as haploinsufficiency. This imbalance can disrupt brain development and function, even without the presence of tumors.

In the study, researchers explored whether blocking the pathway responsible for neurofibromin degradation could restore its levels. Using genetic tools and mouse models of NF1, they identified a pathway that accelerates neurofibromin breakdown. By genetically inhibiting this pathway, they observed significant improvements in behaviors related to impulsivity, hyperactivity, and social interactions—traits commonly associated with autism and ADHD.

This innovative approach demonstrates that increasing the availability of neurofibromin may help mitigate neurobehavioral symptoms in NF1. The researchers believe this strategy could be applicable to over 700 other rare diseases caused by similar genetic haploinsufficiency.

Looking ahead, efforts are underway to identify pharmacological agents that can safely elevate neurofibromin levels and correct disease symptoms. Future studies will also focus on developing effective delivery methods for potential therapies, paving the way for human clinical trials.

These findings open new avenues for targeted treatments in genetic neurodevelopmental disorders, offering hope for improved quality of life in affected individuals.

Source: https://medicalxpress.com/news/2025-07-edge-treatment-approach-neurobehavioral-symptoms.html