An international team investigated the utility of gene therapy for the treatment of dilated cardiomyopathy (DCM) in PGM1-associated congenital glycosylation disorder (PGM1-CDG). Four of the six patients examined for this study had DCM with significantly reduced left ventricular ejection fraction (10-45%) in three of them.
The investigators developed a novel conditional PGM2 (ortholog of human PGM1) cardiomyocyte-specific tamoxifen-inducible mouse model. These mice show a phenotype comparable to that of patients (fibrosis, dilatation of the ventricles, myofibrillar disorganisation, etc.) and a virtual absence of PGM2 protein in the cardiac tissue.
After injection of a dose of gene therapy (AAV9-PGM1) into the tail vein of mice, the analyses reveal :
- a halt in the progression of DCM in the case of a treatment started after the onset of the events;
- no development of DCM, fibrosis or glycogen accumulation when treatment was started before induction with tamoxifen.
These data demonstrate the possibility of correcting or even preventing the cardiac phenotype in PGM1-CDG by increasing PGM1 in the heart.
