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

AbstractPelizaeus –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 le ad 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 oligodendrocy te 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 keton e bodies, that readily enter the brain, can circumvent the requirement of a disrupted blood–brain barrier in the treatment of myelin disease.
Source: Acta Neuropathologica - Category: Neurology Source Type: research