Abstract
Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy, affecting 1 in 2,500 people. The only treatment currently available is rehabilitation or corrective surgery. The most frequent form of the disease, CMT-1A, involves abnormal myelination of the peripheral nerves. Here we used a mouse model of CMT-1A to test the ability of ascorbic acid, a known promoter of myelination, to correct the CMT-1A phenotype. Ascorbic acid treatment resulted in substantial amelioration of the CMT-1A phenotype, and reduced the expression of PMP22 to a level below what is necessary to induce the disease phenotype. As ascorbic acid has already been approved by the FDA for other clinical indications, it offers an immediate therapeutic possibility for patients with the disease.
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Acknowledgements
V.S. was a fellow of the Association Française contre les Myopathies (AFM), and P.N.-F. received support from the American Charcot-Marie-Tooth Association. This work was supported by an AFM grant. We thank CMT France for their constant support; L. Colleaux, N. Levy, M. Mitchell, F. Thomas and L. Villard for their critical reading of the manuscript; and UMAGT and A. Margotat for technical help with the real-time PCR experiments.
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A patent was deposited July 2002, approved in France (PCT in progress), by Université de la Méditerranée, INSERM and AFM. E.P., V.S., J.C.N. and M.F. are the discoverers.
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Passage, E., Norreel, J., Noack-Fraissignes, P. et al. Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease. Nat Med 10, 396–401 (2004). https://doi.org/10.1038/nm1023
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DOI: https://doi.org/10.1038/nm1023
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