Neurofibromatosis type 1 (NF1) is a common neurological disorder caused by mutations in the gene encoding neurofibromin with a prevalence of approximately 1 in 3,500 people. Cognitive deficits such as learning disabilities and attention disorders are present in 40%-60% of NF1 cases and are a significant cause of lifetime morbidity in this population. Mouse models of NF1 show learning deficits similar to those seen in NF1 patients. Dr. Alcino Silva and a team of researchers in his laboratory at the University of California, Los Angeles (UCLA) demonstrated in a mouse model of NF1 that mice exhibit impairments in long-term potentiation, a cellular process underlying learning and memory, and have increased activity of the protein p21 Ras in their brains. Dr. Silva's research team found that lovastatin, a drug commonly used to treat high cholesterol, decreased the excess levels of p21 Ras in the brains NF1 mutant mice. Furthermore, lovastatin treatment was able to rescue the long-term potentiation deficits seen in the mice and reverse their spatial learning and attention deficits. Lovastatin as a treatment for NF1-associated learning disabilities is currently in Phase I clinical trials in adults at UCLA and in children at the Children's National Medical Center in Washington, DC. Investigators are hopeful that lovastatin will prove to be a safe and effective treatment that will improve the quality of life of those with NF1.
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Costa R, Federov NB, Kogan J, et al. 2002. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415:526-539.