Statins, bone, and neurofibromatosis type 1
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BioMed Central
Open Access
Commentary
Statins, bone, and neurofibromatosis type 1 Bruce R Korf Address: Department of Genetics, University of Alabama at Birmingham, 1530 Third Avenue South, Kaul 230, Birmingham, AL, USA Email: Bruce R Korf - [email protected]
Published: 31 July 2008 BMC Medicine 2008, 6:22
doi:10.1186/1741-7015-6-22
Received: 24 June 2008 Accepted: 31 July 2008
This article is available from: http://www.biomedcentral.com/1741-7015/6/22 © 2008 Korf; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Neurofibromatosis type 1 (NF1) is a dominantly inherited multi-system disorder. Major features include pigmentary abnormalities, benign tumors of the nerve sheath (neurofibromas), malignant tumors, learning disabilities, and skeletal dysplasia. The NF1 gene functions as a tumor suppressor, but haploinsuffiency probably accounts for some aspects of the non-tumor phenotype. The protein product, neurofibromin, is a Ras GTPase-activating protein, and various Ras pathway inhibitors are being tested in preclinical models and clinical trials for effectiveness in treating NF1 complications. This month in BMC Medicine, a paper by Kolanczyk et al describes a preclinical mouse model for tibial dysplasia and provides evidence that the drug lovastatin – in use to treat cardiovascular disease – may be beneficial, opening the door to clinical trials in humans.
Patients with neurofibromatosis type 1 (NF1) are largely sustained by the hope that advances in research will result in new forms of treatment. The NF1 gene was identified in 1990 and was quickly found to encode a GTPase activating protein (GAP) whose target is the oncoprotein Ras. However, despite great progress in the dissection of cell signaling pathways involved in the disorder, there is still no definitive treatment to prevent or reverse the complications. The path from bench to bedside may be the best approach, but the challenges should not be underestimated. There are, however, recent signs that provide hope that this approach will pay off. The paper by Kolanczyk et al published this month in BMC Medicine describes a preclinical mouse model for one of the most difficult NF1 lesions to treat, tibial dysplasia, and provides evidence that an existing drug with a known safety profile in children, lovastatin, may be beneficial, opening the door to clinical trials in humans. NF1 poses a particular challenge given the complex and highly variable phenotype [1]. The condition is one member of a group of disorders collectively referred to as 'neu-
rofibromatoses', which includes NF1, NF2, and schwannomatosis. Each is associated with a distinct spectrum of nerve sheath tumors, and each is dominantly transmitted, due to mutation in a different gene. The hallmark lesion of NF1 is the neurofibroma, a benign t
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