Lovastatin as treatment for neurocognitive deficits in neurofibromatosis type 1: phase I study.

In a neurofibromatosis type 1 murine model, treatment with lovastatin reversed cognitive disabilities. We report on a phase I study examining the safety and tolerability of lovastatin in children with neurofibromatosis type 1. Twenty-four children with neurofibromatosis type 1 underwent a dose-escalation protocol for 3 months to identify the maximum tolerated dose and potential toxicity. Minimal side effects were evident, and no child experienced dose-limiting toxicity. Cognitive evaluations were completed before and after treatment, and the results suggested improvement in areas of verbal and nonverbal memory. Additional analyses, using reliable change indices, indicated improvements exceeding those of test-retest or practice effects in some participants. These observations may be analogous to the improvements observed in a neurofibromatosis type 1 murine model treated with lovastatin, although further study and replication are required. The safety and preliminary cognitive results support the need for a larger phase II trial in this population.