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NF1 Learning Disabilities – Key Clinical Trial Published; New Molecular Cause Identified

By September 20, 2011December 18th, 2023Awareness, Science & Research

Learning disabilities, ranging from mild to severe, may affect as many as two-thirds of those with NF1.  These learning disabilities were poorly understood for a long time, until around six years ago when groundbreaking research from the lab of Dr. Alcino Silva (UCLA) showed that the drug Lovastatin, traditionally prescribed for cholesterol lowering, appeared to correct NF1-related learning disabilities in mice genetically engineered to have these deficits.

Over the past few years, Dr. Maria Acosta (Children’s National Medical Center) and her colleagues have taken on the daunting task of translating this ‘mouse result’ to humans, by bringing Lovastatin to clinical trials to treat NF1-related learning disabilities. Dr. Acosta has now published the outcome of this trial in the journal Pediatric Neurology. This was a Phase I study (Phase I studies are designed to assess the safety of the drug). 24 children received Lovastatin over a three-month period,  and no safety issues were seen. Furthermore, and although this study was not designed to fully evaluate the effect of the drug,  the children on the study showed overall improvements in verbal and non-verbal memory functions. These exciting findings will pave the way to the Phase II trial in which the potential efficacy of Lovastatin will be thoroughly evaluated in a larger population.

Looking ahead, researchers will  wish to identify additional approaches for the treatment of NF1 learning disabilities, and this will require identification of further drug targets. Current Children’s Tumor Foundation Young Investigator Award recipient Dr. Jean Gouzi has done just this.  Dr. Gouzi is studying a molecular signaling element termed Anaplastic Lymphoma Kinase (Alk) – a molecule that is dysregulated in and associated with a number of cancers. Dr. Gouzi (jointly of Harvard Medical School/MGH and the Biomedical Sciences Research Center Alexander Fleming, Vari, Greece) is using genetically engineered Drosophila (fruit flies) as a study model. Genetically increasing the activity of Drosophila Alk (dAlk)  in the fly reduced learning ability; and reducing the level of dAlk improved learning behavior. This suggests that dAlk in its normal active state is an inhibitor of learning.  Dr. Gouzi went on to show that dAlkinteracts functionally with Drosophila NF1 (dNf1) and the two molecules dAlk and dNf1 colocalize in the fly. Furthermore, in flies genetically engineered  to have overactive Nf1,  learning is inhibited; however, blocking function of dAlk in these dNf1 mutant flies can compensate for this and normalize learning capabilities.  This experiment suggests that dAlk is a key regulator of dNf1 function and that targeting and inhibiting dAlk function could be a rational approach for the treatment of NF1-related learning disabilities.  Dr. Gouzi’s work is published in the September issue of the online journal PLOS Genetics and will shortly be available free at