Recent studies in mice have begun to elucidate the underlying molecular basis of NF1. Patients with NF1 exhibit decreased levels of Neurofibromin, resulting in excessive p21Ras activity and leading to impairments in long-term potentiation.

INNOVATION:  Researchers at UCLA have succeeded in reversing the learning and memory deficits associated with NF1 in an animal model using statins which are HMG-CoA reductase inhibitors. The unregulated activation of p21Ras is central to the genesis of NF1. Experiments show that statins decrease cellular levels of activated p21Ras. The treatment of NF1 mice using statins resulted in their improved cognitive capabilities when compared to NF1 mice treated with a placebo. In particular, attention deficits and learning, memory and spatial impairments improved to levels comparable to those of wild-type mice. Statins for the treatment of other diseases have been tested extensively in humans with a very low incidence of side effects, suggesting the clinical practicality of the use of statins as a therapy for NF1 related cognitive disorders.

POTENTIAL APPLICATIONS 

• Statins may be used to treat learning and attention deficits associated with NF1.
• The protocol may be used to treat other cognitive disorders including Down Syndrome, autism, ADHD and others.

ADVANTAGES

• Statins can reverse the learning and attention deficits associated with NF1.
• There are currently no other treatments for NF1-associated learning disorders.
• The safety of statins has been established for the treatment of hyperlipidemia.

DEVELOPMENT-TO-DATE:  Currently, 150 adult and child subjects are in the process of being recruited for clinical trials to be conducted in the Netherlands, Washington D.C., and Los Angeles. Adult subjects will be tested with statins in Los Angeles. Adult response to the medication will be measured with neuropsychological test battery at baseline, after stabilization on initial dose, and after titration to increased dose. Pilot trials will end in one year. Full clinical trials will end in 3-4 years.

RELATED PAPERS Weidong L, Cui Y, Kushner SA, Brown RAM, Jentsch DJ, Frankland PW, Cannon TD, Silva AJ. The HMG-CoA Reductase Inhibitor Lovastatin Reverses the Learning and Attention Deficits in a Mouse Model of Neurofibromatosis Type 1. Current Biology,Vol 15, 1961-1967 (2005). more... Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, Ohno M, Kucherlapati R, Jacks T, Silva AJ. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415, 526-30 (2002). more...

Reference: UCLA Case No. 2004-598

US Patent Number: WO2005120496