Antibody formation and mannose-6-phosphate receptor expression impact the efficacy of muscle-specific transgene expression in murine Pompe disease.

ABSTRACT:

Background

Lysosomal storage disorders such as Pompe disease can be more effectively treated, if immune tolerance to enzyme or gene replacement therapy can be achieved. Alternatively, immune responses against acid α-glucosidase (GAA) might be evaded in Pompe disease through muscle-specific expression of GAA with adeno-associated virus (AAV) vectors.

Methods

An AAV vector containing the MHCK7 regulatory cassette to drive muscle-specific GAA expression was administered to GAA knockout (KO) mice, immune tolerant GAA-KO mice and mannose-6-phosphate deficient GAA-KO mice. GAA activity and glycogen content were analyzed in striated muscle to determine biochemical efficacy.

Results

The biochemical efficacy from GAA expression was slightly reduced in GAA-KO mice, as demonstra

SUBMITTER: Sun B 

PROVIDER: S-EPMC3655728 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature