Researchers from China and the Netherlands developed a new hematopoietic stem cell-mediated lentiviral gene therapy (HSPC-LVGT) that showed promising results in a mouse model of Pompe disease. Based on their results, the researchers said the new transgene could be further developed as a potential gene therapy for Pompe disease. 

The team has previously shown that HSPC-LVGT can lead to a reduction in glycogen in the heart, skeletal muscles, and partially the brain. However, the uptake of the therapy was limited.

Here, researchers led by Pim Pijnappel, PhD, from Erasmus University Rotterdam, fused insulin-like growth factor 2 (IGF2) to a codon-optimized version of the GAA gene, which they called IGF2.GAA, to improve cellular uptake. 

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The study is published in the journal Molecular Therapy-Methods & Clinical Development.

They found that this new approach led to a complete normalization of glycogen levels and impaired autophagy at a clinically relevant vector copy number in the heart and skeletal muscles of the mice. The researchers reported that the new gene therapy was particularly effective in treating the central nervous system. 

“These results identify IGF2.GAA as a candidate transgene for future clinical development of HSPC-LVGT for Pompe disease,” they wrote.

Pompe disease is caused by a mutation in the GAA gene, leading to a deficiency in the GAA enzyme, the role of which is to cleave glycogen to form glucose. GAA deficiency results in the accumulation of glycogen in different tissues causing damage, especially in the heart and skeletal muscles.

Enzyme replacement therapy can improve cardiac, respiratory, and motor function, but is poorly taken up by cells and cannot cross the blood-brain barrier. Gene therapy has emerged as a potential new avenue for the treatment of the disease.


Liang Q, Catalano F, Vlaar EC, et al. IGF2-tagging of GAA promotes full correction of murine Pompe disease at a clinically relevant dosage of lentiviral gene therapy. Mol Ther Methods Clin Dev. Published online September 24, 2022. doi: 10.1016/j.omtm.2022.09.010