Potential first gene therapy for correcting the rare disease human phosphoglucomutase I (PGM1) Deficiency

The only therapy currently is dietary galactose supplementation, which alone cannot fully correct all disease phenotypes, especially the lethal cardiomyopathy. Long-term galactose supplementation in patients may pose additional risks.

Human PGM1 deficiency is a debilitating, not to mention potentially lethal genetic disorder. A novel gene therapy has the potential to cure those suffering from PGM1 deficiency. An AAV9-gene therapy approach addresses the root cause of the disorder by augmenting the missing PGM1 activity in PGM1-deficient cells. Further, in PGM1 deficient animals, cardiac expression of the PGM1 helps cardiomyopathy in the mouse model.

Optimization & Testing

• Potential as first FDA approved treatment or cure for PGM1 deficiency.
• AAV9 backbone proven safe in clinical trials and has led to FDA approvals for other genetic disorders.
• Other subsets of patients who do not respond to supplements such as d-galactose may be candidates.

Balakrishnan, Bijina et al. “A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality.” Journal of inherited metabolic disease vol. 42,5 (2019): 998-1007. doi:10.1002/jimd.12110

Balakrishnan B et al. AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase 1 deficiency (PGM1-CDG). Transl Res. 2023;257:1-14. doi:10.1016/j.trsl.2023.01.004

Aaron Duffy
(801) 585-1377
aaron.duffy@utah.edu