In 2005, the research team headed by Dr. Alcino Silva at the University of California Los Angeles gave us, through a series of elegant studies in mice, the first demonstration that the drug Lovastatin might be a treatment for NF1 learning disabilities. This research informed clinical thinking in this area and led to a currently ongoing Phase II clinical trial of Lovastatin in children with NF1 learning disabilities. Now the group has further unraveled the molecular basis of learning disabilities in NF1. The findings are published this week * in the Proceedings of the National Academy of Sciences in a study led by Carrie Shilyansky, and conducted while she was a recent Young Investigator Award recipient of the Children’s Tumor Foundation. Here, the group looks more closely into working memory – the way that we manage and prioritize information and tasks as they arise. A region of the brain called prefrontal cortex is normally very important in working memory activity. The researchers show that in mice with NF1 learning disabilities, the prefrontal cortex is over-inhibited due to changes in neurotransmitter release that are caused by lack of functional neurofibromin (protein made by the NF1 gene). The group then moved to the clinic and gave working memory-based tasks to a population of people with NF1 learning disabilities, and found blunted activation of prefrontal cortex and striatum, a direct marker of working memory impairments characteristic of NF1 and demonstrating the same as had been seen in the mice. As well as enhancing our understanding of what is actually changed in the brain in NF1 learning disabilities this research gives further credibility to the NF1 mouse model of learning disabilities as a valuable resource for testing further drugs that might improve NF1 learning disabilities and like Lovastatin make their way to the clinic.
* Shilyansky et al. (2010) Neurofibromin regulates corticostriatal inhibitory networks during working memory performance. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13141-6. Epub 2010 Jul 12
