SK. Stumpf, SA. Berghoff, A. Trevisiol, L. Spieth, T. Düking, LV. Schneider, L. Schlaphoff, S. Dreha-Kulaczewski, A. Bley, D. Burfeind, K. Kusch, M. Mitkovski, T. Ruhwedel, P. Guder, H. Röhse, J. Denecke, J. Gärtner, W. Möbius, KA. Nave, et al. (2019). Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease. Acta neuropathologica, 138(1), 147-161. https://doi.org/10.1007/s00401-019-01985-2

PubMed 30919030

[Abstract]
Pelizaeus-Merzbacher disease (PMD) is an untreatable and fatal leukodystrophy. In a model of PMD with perturbed blood-brain barrier integrity, cholesterol supplementation promotes myelin membrane growth. Here, we show that in contrast to the mouse model, dietary cholesterol in two PMD patients did not lead to a major advancement of hypomyelination, potentially because the intact blood-brain barrier precludes its entry into the CNS. We therefore turned to a PMD mouse model with preserved blood-brain barrier integrity and show that a high-fat/low-carbohydrate ketogenic diet restored oligodendrocyte integrity and increased CNS myelination. This dietary intervention also ameliorated axonal degeneration and normalized motor functions. Moreover, in a paradigm of adult remyelination, ketogenic diet facilitated repair and attenuated axon damage. We suggest that a therapy with lipids such as ketone bodies, that readily enter the brain, can circumvent the requirement of a disrupted blood-brain barrier in the treatment of myelin disease.