Sign in Subscribe
Diseases

Long-Term Efficacy of Gene Therapy in Glycogen Storage Disease Type III

Strategic Insights

— 1 min read

Scientists at Duke University have made significant progress in developing a gene therapy approach for glycogen storage disease type III (GSD III) using a recombinant adeno-associated virus serotype 9 (AAV9) vector. This innovative therapy, which expresses a bacterial debranching enzyme (pullulanase) driven by a tandem dual promoter, has shown long-term efficacy in GSD IIIa mice. The study, led by researchers at Duke University School of Medicine, demonstrates the potential of this gene therapy approach in correcting the disease's symptoms and improving muscle function.

Key Takeaways:

  • The gene therapy approach using AAV9-Dual-Pull expression led to persistent pullulanase expression in the liver, heart, and skeletal muscle, accompanied by glycogen reduction and reversal of liver fibrosis.
  • The AAV-LSP-Pull treatment showed a better therapeutic efficacy in the liver but had no effect on cardiac and skeletal muscles.
  • Behavioral tests revealed long-term improvement of muscle function in GSD IIIa mice treated with AAV-Dual-Pull.
  • The study concluded that future studies will test this gene therapy approach in GSD IIIa dogs prior to clinical translation to humans.
  • The research was supported by Duke University and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
  • The study's results were published in the journal Advances in Cell and Gene Therapy in 2025.

Statistics:

  • 2.5 × 10^10 viral genome copies (vg/kg) were used for both AAV9-LSP-Pull and AAV9-Dual-Pull treatments.
  • The study involved 3-month-old GSD IIIa mice that were intravenously injected with the AAV vectors.
  • Liver and muscle enzymes in plasma and disease biomarkers in urine were analyzed at multiple time points from 3 to 12 months after treatment.
  • The study found that AAV-Dual-Pull treatment led to a 75% reduction in glycogen content in the liver, heart, and skeletal muscle at 9 months post-treatment.
  • Muscle function tests revealed a significant improvement in GSD IIIa mice treated with AAV-Dual-Pull at 12 months post-treatment.

Sources:

  • NewsRx. Researchers from Duke University School of Medicine Describe Findings in Cell and Gene Therapy (Long-Term Correction of Murine Glycogen Storage Disease Type III by AAV-Mediated Gene Therapy Using an Immunotolerizing Dual Promoter to Express ...). Biotech Week. October 22, 2025; p 225.
  • Long-Term Correction of Murine Glycogen Storage Disease Type III by AAV-Mediated Gene Therapy Using an Immunotolerizing Dual Promoter to Express Bacterial Pullulanase. Advances in Cell and Gene Therapy, 2025;2025(1).

Read more