25 Nov Neurofibromatosis: Simvastatin for Cognitive Deficits
MedicalResearch.com: What are the main findings of the study?
Answer: Research in genetic mouse models suggested that inhibition of HMG-CoA-reductase by statins might ameliorate the cognitive and behavioral phenotype of children with Neurofibromatosis type 1 (NF1), an autosomal dominant disorder. In a 12-month randomized placebo-controlled study including 84 children with NF1, we found that simvastatin, an inhibitor of the HMG-CoA-reductase pathway had no effect on full-scale intelligence, attention problems or internalizing behavioral problems, or on any of the secondary outcome measures.
MedicalResearch.com: Were any of the findings unexpected?
Answer: A previous, smaller, randomized study with simvastatin was already largely negative, although that study was limited in treatment duration to 12-weeks. One secondary outcome measure was significantly better in the treatment-arm compared to placebo. A 12-week study of lovastatin, a very similar drug, found improvements, but that study had no control group. Hence, our results were disappointing, but not entirely unexpected.
MedicalResearch.com: What should clinicians and patients take away from your report?
Answer: Simvastatin should not be prescribed for treating cognitive or behavioral issues in NF1 at this point.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Answer: We advocate further investigations into the pathophysiology of the cognitive deficits in NF1, as new clues may result in developing novel treatments. In particular it is of importance to understand how NF1 selectively affects GABA-ergic neurons. Our trial further emphasizes the need for randomized placebo-controlled trials and the use of outcome measures that are of direct relevance to the patient, when doing cognitive trials.
Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): a randomised, placebo-controlled trial behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): a randomised, placebo-controlled trial.
Department of Neuroscience, Erasmus University Medical Centre, Rotterdam, Netherlands; Department of Paediatrics, Erasmus University Medical Centre, Rotterdam, Netherlands; ENCORE Expertise Centre For Neurodevelopmental Disorders, Erasmus University Medical Centre, Rotterdam, Netherlands.