An investigational gene therapy with an adeno-associated virus serotype 8 vector (AAV8-LSPhGAA) appears to be safe and bioactive in patients with Pompe disease, according to results from a phase 1 clinical trial published in Molecular Therapy. The study also showed that withdrawing from enzyme replacement therapy following the potential gene therapy was safe. These findings “justify continued clinical development of AAV8-LSPhGAA therapy in Pompe disease,” the authors of the study concluded.

The results came from 3 patients with late-onset Pompe disease who were treated with the experimental gene therapy as part of the 52-week, open-label, single-dose, dose-escalation study. 

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After 26 weeks, high levels of acid α-glucosidase (GAA) activity were detected in the serum of the patients and no clinically significant declines were reported. Therefore, enzyme replacement therapy was stopped. 

From week 4 of the study, prednisone was successfully used as immunoprophylaxis and tapered over the next 11 weeks.

All 3 patients had sustained GAA activity 2 weeks following the last dose of enzyme replacement therapy. No treatment-related serious adverse events were reported, and none of the patients had anticapsid T-cell responses that decreased the expression of the transgene. 

However, when they analyzed the muscle biopsies of the patients at week 24, the researchers saw that glycogen content remained the same in 2 of the patients, but the activity of the GAA enzyme was significantly increased at 52 weeks.

Pompe disease is a rare disease characterized by the deficiency or absence of the GAA enzyme due to a mutation in the gene that encodes it. The role of the GAA enzyme is to cleave glycogen to form glucose, so patients with Pompe disease have glycogen accumulation in their tissues.

Gene therapy with AAV8-LSPhGAA aims to create a liver depot for GAA, thereby eliminating the need for enzyme replacement therapy in patients with Pompe disease.


Smith EC, Hopkins S, Case LE, et al. Phase I study of liver depot gene therapy in late-onset Pompe disease. Mol Ther. Published online February 18, 2023. doi:10.1016/j.ymthe.2023.02.014

AAV2/8-LSPhGAA (ACTUS-101) in late-onset Pompe disease. May 23, 2018. Updated May 31, 2022. Accessed March 8, 2023.