Fc-Modified IVIG with Enhanced Blood-Brain Barrier Penetration Ameliorates Cognitive Deficits and Neuropathology in A53T α-Synuclein Transgenic Mice.

ABSTRACT: Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by degeneration of nigrostriatal dopaminergic neurons together with α-synuclein (α-syn) aggregation, neuroinflammation, and oxidative stress. Although intravenous immunoglobulin (IVIG) contains naturally occurring antibodies against α-syn oligomers, it has failed to demonstrate therapeutic efficacy in PD models, likely due to limited delivery across the blood-brain barrier (BBB). Enhancing BBB penetration of IVIG could therefore substantially improve its therapeutic potential in PD. Here, we developed a brain-targeted IVIG formulation (IVIGᴬ) by site-specifically conjugating Angiopep-2 (Ang-2) to the Fc glycan site (Asn297) of IVIG, enabling receptor-mediated transcytosis across the BBB via low-density lipoprotein

SUBMITTER: Zhu J 

PROVIDER: S-EPMC12618800 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature