Gene replacement therapy for Piga GPI-anchor deficiency in the developing nervous system.

ABSTRACT: Glycosylphosphatidylinositol (GPI) anchors are a class of post-translational modifications observed on over 150 proteins. Pathogenic variants in the GPI biosynthesis enzyme, PIGA, in humans are associated with several brain anomalies such as hypomyelination, cerebellar hypoplasia, ataxic gait, and can lead to premature mortality. We previously genetically deleted Piga from the embryonic mouse brain which led to early postnatal death and significant structural brain malformations similar to those observed in humans with PIGA variants. The current treatment options for PIGA patients only manage symptoms and provides palliative care, demonstrating a need for new therapeutic options. We employed an AAV9-mediated PIGA gene-replacement (AAV9-hPIGA) strat

SUBMITTER: Watts JL 

PROVIDER: S-EPMC12710646 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature