Intermittent lipid nanoparticle mRNA administration prevents cortical dysmyelination associated with arginase deficiency.

ABSTRACT: Arginase deficiency is associated with prominent neuromotor features, including spastic diplegia, clonus, and hyperreflexia; intellectual disability and progressive neurological decline are other signs. In a constitutive murine model, we recently described leukodystrophy as a significant component of the central nervous system features of arginase deficiency. In the present studies, we sought to examine if the administration of a lipid nanoparticle carrying human ARG1 mRNA to constitutive knockout mice could prevent abnormalities in myelination associated with arginase deficiency. Imaging of the cingulum, striatum, and cervical segments of the corticospinal tract revealed a drastic reduction of myelinated axons; signs of degenerating axons were also present with thin myelin layers.

SUBMITTER: Khoja S 

PROVIDER: S-EPMC9156989 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature