Galectin3: a novel biomarker of glycogen storage disease type III

Glycogen storage disease type III (GSDIII) is a rare genetic disease caused by mutations in the AGL gene, resulting in glycogen debranching enzyme (GDE) deficiency. There is currently no cure. Among various symptoms, skeletal muscle impairment represents a key target for the development of therapies. Identifying reliable biomarkers is crucial for evaluating new therapies, yet muscle-specific biomarkers for GSDIII are lacking. In this study, we generated GSDIII skeletal muscle cells derived from human-induced pluripotent stem cells that recapitulate the glycogen accumulation phenotype. A comparative gene expression analysis was carried out using RNA sequencing to identify novel biomarkers. Our results reports a significant overexpression of galectin-3 in both human and mouse models and patient biopsies, and a significant decrease in mice treated by an AAV gene therapy. Together, our results propose galectin-3 as a biomarker to assess therapeutic efficacy and GSDIII pathological monitoring in the muscle. we performed a bulk RNA sequencing of the 3 CTRLs and the 4 GSDIIIPatients generated skMt. (Quantseq)