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Statin Therapy and Cognitive Deficits Associated With Neurofibromatosis Type 1—Reply
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In Reply: Dr Jansen raises questions about the rationale of our trial and the value of the NF1 mouse model for translational research.1 It is important to re-emphasize that the NF1 protein is not involved in cholesterol metabolism. NF1 is a negative regulator of RAS activity, and increased RAS signaling has been shown to underlie the learning deficits of Nf1+/– mice.2 The rationale to treat the cognitive deficits with statins was based on 2 fundamental findings in the cancer literature: RAS requires posttranslational isoprenylation for proper signaling, and RAS transforming activity can be suppressed by reducing the synthesis of the isoprenyl groups by statins.1, 3-4 The molecular and behavioral deficits of Nf1+/– mice can indeed be ameliorated by decreasing RAS activity, either genetically or by administrating farnesyl transferase inhibitors or statins.1-2
The pharmacokinetic profile of simvastatin was carefully considered in our study design. Patients and their general practitioners were counseled to . . . [Full Text of this Article]
Ype Elgersma, PhD
y.elgersma@erasmusmc.nl
Lianne C. Krab, MSc;
Henriëtte A. Moll, MD, PhD
Erasmus MC University Medical Center
Rotterdam, the Netherlands
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RELATED LETTER
Statin Therapy and Cognitive Deficits Associated With Neurofibromatosis Type 1
Jacobus F. A. Jansen
JAMA. 2008;300(20):2369.
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