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Transcriptomic profile of skeletal muscle in wild-type, GAA knock-out, and AAV treated GAA knock-out mice to understand Pompe disease mechanisms and assess therapeutic efficacy

ABSTRACT: Pompe disease (glycogen storage disease type II, or acid maltase deficiency) is an autosomal-recessive disorder of metabolism caused by mutations in the lysosomal hydrolase, acid alpha-glucosidase gene (GAA), resulting in progressive muscle atrophy. Gene therapy is a promising approach to treat genetic diseases, and liver-restricted expression of secretable GAA can produce immune tolerance and improve muscle GAA activity. To further understand the molecular mechanisms underlying Pompe disease and impact of gene therapy, we applied RNA sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE159063 | GEO | 2020/10/06

REPOSITORIES: GEO

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GAA deficiency (Pompe Disease) in infantile-onset patients

Project description:Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease.

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Skeletal muscle gene expression in the wild type and the GAA knock-out mice, a model of Pompe disease

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Rescue of advanced Pompe disease in mice with hepatic expression of secretable acid α-glucosidase

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2011-02-17 | E-GEOD-27280 | biostudies-arrayexpress

Transcriptomic profile of skeletal muscle in wild-type, GAA knock-out, and AAV treated GAA knock-out mice to understand Pompe disease mechanisms and assess therapeutic efficacy

Project description:Transcriptomic profile of skeletal muscle in wild-type, GAA knock-out, and AAV treated GAA knock-out mice to understand Pompe disease mechanisms and assess therapeutic efficacy

| PRJNA667501 | ENA

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