Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease

2019 | journal article. A publication with affiliation to the University of Göttingen.

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​Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease​
Stumpf, S. K.; Berghoff, S. A.; Trevisiol, A. ; Spieth, L.; Düking, T.; Schneider, L. V. & Schlaphoff, L. et al.​ (2019) 
Acta Neuropathologica138(1) pp. 147​-161​.​ DOI: 

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Stumpf, Sina K.; Berghoff, Stefan A.; Trevisiol, Andrea ; Spieth, Lena; Düking, Tim; Schneider, Lennart V.; Schlaphoff, Lennart; Dreha-Kulaczewski, Steffi ; Bley, Annette; Burfeind, Dinah; Kusch, Kathrin ; Mitkovski, Miso; Ruhwedel, Torben; Guder, Philipp; Röhse, Heiko; Denecke, Jonas; Gärtner, Jutta ; Möbius, Wiebke ; Nave, Klaus-Armin ; Saher, Gesine
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.
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Acta Neuropathologica 
0001-6322; 1432-0533



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