The Autophagic Activator GHF-201 Can Alleviate Pathology in a Mouse Model and in Patient Fibroblasts of Type III Glycogenosis.

Glycogen storage disease type III (GSDIII) is a hereditary glycogenosis caused by deficiency of the glycogen debranching enzyme (GDE), an enzyme, encoded by , enabling glycogen degradation by catalyzing alpha-1,4-oligosaccharide side chain transfer and alpha-1,6-glucose cleavage. GDE deficiency causes accumulation of phosphorylase-limited dextrin, leading to liver disorder followed by fatal myopathy. Here, we tested the capacity of the new autophagosomal activator GHF-201 to alleviate disease burden by clearing pathogenic glycogen surcharge in the GSDIII mouse model .

Essential dextrin structure as donor substrate for 4-α-glucanotransferase in glycogen debranching enzyme.

Glycogen debranching enzyme is a single polypeptide with distinct catalytic sites for 4-α-glucanotransferase and amylo-α-1,6-glucosidase. To allow phosphorylase to degrade the inner tiers of highly branched glycogen, 4-α-glucanotransferase converts the phosphorylase-limit biantennary branch G-G-G-G-(G-G-G-G↔)G-G- (G: d-glucose, hyphens: α-1,4-linkages; double-headed arrow: α-1,6-linkage) into the G-G-G-G-(G↔)G-G- residue, which is then subjected to amylo-α-1,6-glucosidase to release the remaining G↔ residue. However, while the essential side-chain structure of the 4-α-glucanotransferase donor substrate has been determined to be the G-G-G-G↔ residue (Watanabe, Y.

Toward an Understanding of GSD5 (McArdle disease): How Do Individuals Learn to Live with the Metabolic Defect in Daily Life.

Background: Glycogen storage disease type 5 (GSD) is an autosomal recessive inherited metabolic myopathy caused by a deficiency of the enzyme muscle glycogen phosphorylase. Individuals with GSD5 experience physical activity intolerance.

Objective: This patient-led study aimed to capture the daily life experiences of GSD5, with a focus on adapting to and coping with their physical activity intolerance.

In vivo characterization of glycogen storage disease type III in a mouse model using glycoNOE MRI.

Purpose: Glycogen storage disease type III (GSD III) is a rare inherited metabolic disease characterized by excessive accumulation of glycogen in liver, skeletal muscle, and heart. Currently, there are no widely available noninvasive methods to assess tissue glycogen levels and disease load. Here, we use glycogen nuclear Overhauser effect (glycoNOE) MRI to quantify hepatic glycogen levels in a mouse model of GSD III.

Generation of three induced pluripotent stem cell lines from patients with glycogen storage disease type III.

Glycogen storage disease type III (GSDIII) is an autosomal recessive disorder characterized by a deficiency of glycogen debranching enzyme (GDE) leading to cytosolic glycogen accumulation and inducing liver and muscle pathology. Skin fibroblasts from three GSDIII patients were reprogrammed into induced pluripotent stem cells (iPSCs) using non-integrated Sendai virus. All of the three lines exhibited normal morphology, expression of pluripotent markers, stable karyotype, potential of trilineage differentiation and absence of GDE expression, making them valuable tools for modeling GSDIII disease in vitro, studying pathological mechanisms and investigating potential treatments.