Preclinical dose-finding study with a liver-tropic, recombinant AAV-2/8 vector in the mouse model of galactosialidosis.

ABSTRACT: Galactosialidosis (GS) is a lysosomal storage disease linked to deficiency of the protective protein/cathepsin A (PPCA). Similarly to GS patients, Ppca-null mice develop a systemic disease of the reticuloendothelial system, affecting most visceral organs and the nervous system. Symptoms include severe nephropathy, visceromegaly, infertility, progressive ataxia, and shortened life span. Here, we have conducted a preclinical, dose-finding study on a large cohort of GS mice injected intravenously at 1 month of age with increasing doses of a GMP-grade rAAV2/8 vector, expressing PPCA under the control of a liver-specific promoter. Treated mice, monitored for 16 weeks post-treatment, had normal physical appearance and behavior without discernable side effects. Despite the restricted expression o

SUBMITTER: Hu H 

PROVIDER: S-EPMC3277225 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature