A letter recently published in Nature Medicine reports the role of diet enriched in cholesterol for treatment of Pelizaeus-Merzbacher disease (PMD), a fatal leukodystrophy due to increased dosage of the gene encoding the proteolipid protein 1 (PLP1) .
The major finding of this study is that cholesterol promotes normal trafficking of PLP and PMD mice fed with a cholesterol-enriched diet show restoration of oligodendrocyte numbers and amelioration of intracellular PLP accumulation. Moreover, myelin content was increased, inflammation and gliosis were reduced and motor defects improved. Even after onset of clinical symptoms, cholesterol treatment prevented disease progression. Dietary cholesterol did not reduce PLP overexpression but facilitated incorporation of PLP into myelin membranes. These findings may have implications for therapeutic interventions in patients with PMD.
OMMBID Part 28 NEUROGENETICS chapter 228: Pelizaeus-Merzbacher Disease and the Allelic Disorder X-linked Spastic Paraplegia Type 2.
Saher G, Rudolphi F, Corthals K, Ruhwedel T, Schmidt KF, LÃ¶wel S, Dibaj P, Barrette B, MÃ¶bius W, Nave KA.Therapy of Pelizaeus-Merzbacher disease in mice by feeding a cholesterol-enriched diet. Nat Med. 2012 Jun 17. doi: 10.1038/nm.2833. [Epub ahead of print]PMID: 22706386 [PubMed – as supplied by publisher]
Posted by Nicola Brunetti-Pierri, MD, FACMG