AAV8-LSPhGAA for the treatment of Pompe disease seems to be safe and bioactive, according to results from a phase 1 clinical trial presented at the 2022 Muscular Dystrophy Association Clinical & Scientific Conference.

AAV8-LSPhGAA is a gene therapy that uses adeno-associated virus serotype 8 as a vector to allow the liver to continuously secrete recombinant human GAA enzyme, thereby correcting GAA deficiency. The treatment could eliminate the need for enzyme replacement therapy, the standard treatment for Pompe disease, by creating a liver depot for the production of the GAA enzyme, the researchers said.

The open-label, ascending dose phase 1 trial is testing the safety and bioactivity of AAV2/8-LSPhGAA in 8 adult patients diagnosed with Pompe disease. 

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The primary outcome measures are the incidence of patient-reported treatment-emergent adverse and serious adverse events and the number of participants with abnormal laboratory values. Secondary outcome measures include GAA bioactivity in the muscle and plasma, glycogen content in the muscle, formation of anti-GAA antibodies, muscle status, lung function, and quality of life.

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Here, researchers reported initial results from 3 patients. According to these, there were no treatment-related serious adverse events. However, 1 patient experienced headaches of moderate severity twice. Laboratory assessments supported the safety of AAV8-LSPhGAA.

None of the patients had elevated alanine aminotransferase levels in their serum, meaning that there were no anti-AAV8 T-cell responses.

At week 24 all patients met the criteria to stop enzyme replacement therapy and to remain off it at weeks 52 and 104 although 1 patient restarted it at week 97. At week 24, there was a large decrease in muscle glycogen content for 1 patient as shown by muscle biopsy. Moreover, GAA activity in muscles for all participants was significantly increased compared to baseline at week 52.

“These initial data support the safety and bioactivity of AAV8-LSPhGAA and justify continued clinical development of AAV8-LSPhGAA therapy in Pompe disease,” the researchers concluded.


Smith E, Hopkins S, Case L, et al. Phase 1 of gene therapy in late-onset Pompe disease: analysis of safety, bioactivity, and secondary endpoints. Poster presented at: 2022 Muscular Dystrophy Association Clinical & Scientific Conference; March 13-16, 2022; Nashville, TN. Poster 66.

AAV2/8-LSPhGAA in late-onset Pompe disease. US National Library of Medicine. Updated February 21, 2021. Accessed April 6, 2022.