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

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

doi:10.1007/s00401-019-01985-2

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

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

MPS-Authors

/persons/resource/persons182438

Stumpf, Sina K.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons202532

Berghoff, Stefan A.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182611

Trevisiol, Andrea
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons213399

Spieth, Lena
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons202530

Düking, Tim
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons232121

Schneider, Lennart V.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons232123

Schlaphoff, Lennart
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons232125

Burfeind, Dinah
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182268

Kusch, Kathrin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182305

Mitkovski, Miso
Light microscopy facility, Wiss. Servicegruppen, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182382

Ruhwedel, Torben
Electron microscopy, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons281473

Röhse, Heiko
Light microscopy facility, Wiss. Servicegruppen, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182306

Möbius, Wiebke
Electron microscopy, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182320

Nave, Klaus-Armin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182386

Saher, Gesine
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

Stumpf_19.pdf
(Publisher version), 3MB

Supplementary Material (public)

Correction.pdf
(Supplementary material), 3MB

Citation

Stumpf, S. K., Berghoff, S. A., Trevisiol, A., Spieth, L., Düking, T., Schneider, L. V., et al. (2019). Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease. Acta Neuropathologica, 138, 147-161. doi:10.1007/s00401-019-01985-2.

Cite as: https://hdl.handle.net/21.11116/0000-0003-54FF-0

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.