Pompe disease

As a single-stranded small DNA virus, adeno-associated virus (AAV) can be designed as a gene vector in which genes can be transported to the organism and cure some disease. In recent years, AAV vector owing to its non-toxicity has received extensive attention from research scholars, especially, for the treatment of liver directed disease. For example, pompe disease is a liver genetic disorder which is mainly caused by the congenital lack of acid alpha-glucosidase (GAA) gene in the body. Creative Biolabs provides superior vector design, gene characterization and therapy service, which can contribute to the research and treatment of clinical genetic diseases.

AAV Vector Efficacy Evaluation for Pompe Disease

Pompe disease also called Glycogen storage disease type II, is caused by a congenital deficiency of GAA gene. GAA is usually responsible for the release of monosaccharides, thus, loss of GAA will inevitably lead to malicious accumulation of glycogen, break the contraction of the organ, eventually result in muscle cell contraction, especially cardiomyocytes. More importantly, AAV is widely known to researchers as a carrier for the successful delivery of the GAA gene. This part of the research is mainly divided into the following three aspects for efficacy evaluation:

Schematic of investigational liver-directed gene therapy for Pompe disease. Figure 1. Schematic of investigational liver-directed gene therapy for Pompe disease. (Ronzitti, 2019)

  • GAA Activity

    • GAA activity directly explains the capabilities and quantity of GAA. Byrne found that after 14 days AAV vector gene therapy, GAA activities showed four-fold higher than the control group, with a 10-fold increase observed in GAA-deficient myotubes. More importantly, GAA enzymatic activity was increased over 1.5-fold than non-treatment in the tibialis anterior muscles at 1 week, and this growing trend continued in the next six months of treatment.

  • Glycogen Storage

    • Normal expression of the GAA gene delivered via AAV vector can contribute to the reduction of glycogen. Scientists found that there was a significant reduction of glycogen in the heart, diaphragm and skeletal muscle by light microscopy of periodic acid-Schiff (PAS) stained histologic sections, after 24 weeks AAV2/8 administration, which fully explains the previous point.

  • Diaphragm Contractile Force

    • CathrynMah has designed recombinant AAV serotype 1 (rAAV2/1) vector and showed that the contractile force of cardiomyocytes in the rAAV2/1 treatment group was about twice higher, which confirmed that systemic delivery of a therapeutic rAAV2/1 vector could improve significantly in cardiac conductance. Cardiac and respiratory function can be one of the most powerful persuasion evidences.

Liver-directed gene transfer with AAV vectors induces immunological tolerance. Figure 2. Liver-directed gene transfer with AAV vectors induces immunological tolerance via multiple mechanisms. (Ronzitti, 2019)

With the rapid development of modern gene therapy, AAV provides new ideas and methods for the treatment of pompe disease. Creative Biolabs owns the most cutting-edge research background and research ideas in AAV gene support, providing comprehensive vector design and gene loading, which lays a solid theoretical foundation for the treatment of genetic diseases such as pompe disease. For more information, please feel free to contact us for more details and we are glad to provide you with the best advice.

Reference

  1. Ronzitti, G.; et al. (2019). Progress and challenges of gene therapy for Pompe disease. Annals of Translational Medicine. 7(13): 287-301.
For research use only. Not intended for any clinical use.