Researchers presented a new candidate vector that could potentially be used as an effective therapeutic tool in Pompe disease, as presented at the 18th Annual WorldSymposium 2022.

The ematopoietic stem and progenitor cells transfected with the candidate vector can alleviate cardiomyopathy, muscle weakness, and central nervous system pathology in the long term in a mouse model of the disease.

“We anticipate this approach could translate into a clinical application of single-dose therapy for Pompe disease patients,” the researchers wrote. The lentiviral vector presented here carries a human GAA transgene fused to a glycosylation independent lysosomal targeting tag under a clinically proven promoter.

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The researchers from AVROBIO in Cambridge, Massachusetts, and Hannover Medical School in Germany report supraphysiological GAA enzyme activity levels in the hematopoietic cells transfected with the vector as well as the hearts, skeletal muscles, spinal cords, and brains of the animals transplanted with the genetically modified stem cells at 8 months after transplantation.

Read more about Pompe disease etiology

This leads to a reduction in total hexose tetrasaccharide, glycogen accumulation, and vacuolation in the heart, diaphragm, brain, spinal cord, and most of the skeletal muscles that they tested in the mice, they said.

Moreover, they report that the approach can reverse pathological heart remodeling and improve motor function in the mice. They also report that there is no selection of integrations into proto-oncogenes or clonal dominance.

In Pompe disease, a mutation in the GAA gene leads to the accumulation of glycogen, especially in the heart and skeletal muscles causing weakness due to the dysfunction of the GAA enzyme that is responsible for breaking down glycogen.

Currently, care for Pompe disease is enzyme replacement therapy. However, this can trigger an immune response in the long-term leading to a reduction in efficacy. It is also not able to prevent disease progression. Gene therapy could potentially provide lifelong benefits for patients with the disease.


van Til NP, Schindler, JW, Yoon JK, et al. Long-term hematopoietic stem cell lentiviral gene therapy rescues neuromuscular manifestations in preclinical study of Pompe disease mice. Mol Genet Metab. 2022;135(2):S122-S123. doi:10.1016/j.ymgme.2021.11.326