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

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


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.

Bibliografische Daten

StatusVeröffentlicht - 07.2019
PubMed 30919030