ArticleAnnals of neurology2021
Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications.
Article in Annals of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG).International journal of molecular sciences · 2022Pooled it
- Proteo-Metabolomic Profiling of PMM2-CDG Reveals Dysregulation of Retinoic Acid Synthesis, Myo-Inositol, and the Hexosamine Pathway.Journal of inherited metabolic disease · 2026Article
- Stress-induced secretory pathway disruption causes atypical metalloproteinase transport in PMM2-CDG.iScience · 2026Article
- Repurposing the HMG-CoA reductase inhibitor atorvastatin for SRD5A3-congenital disorder of glycosylation.Communications medicine · 2026Article
- Personalized Drug Repurposing Screen Identifies Patient-Specific Therapeutic Candidates for Mucopolysaccharidosis Type IIIB.Journal of personalized medicine · 2026Article
- Correlation Analysis of Clinical, Imaging, and Genetic Etiologies in Pediatric Hereditary Cerebellar Atrophy: A Single-Center Study.Molecular genetics & genomic medicine · 2026Article
- PMM2 interacts with TRIM28 to recruit E2F4 and promote KIFC3-mediated tumor glycolysis and colorectal cancer progression.Oncogene · 2026Article
- Treatment of Single Patient With PMM2-Congenital Disorder of Glycosylation With Govorestat (AT-007), an Aldose Reductase Inhibitor.JIMD reports · 2025Article
- Further delineation of defects in MRPS2 causing human OXPHOS deficiency and early developmental abnormalities in zebrafish.European journal of human genetics : EJHG · 2025Article
- Resolving Hexose-Phosphates by LC-MS Leads to New Insights in PGM1-CDG Pathophysiology.ACS omega · 2025Article
- Deciphering the Glycoproteomic Landscape of Mood Disorders: Unveiling Molecular Association Between CDG and Depression Resilience.Research square · 2025Article
- Predicting disease-overarching therapeutic approaches for Congenital Disorders of Glycosylation using multi-OMICS.bioRxiv : the preprint server for biology · 2025Article
- Glycosphingolipid synthesis is impaired in SLC35A2-CDG and improves with galactose supplementation.Cellular and molecular life sciences : CMLS · 2025Article
- Novel mouse model reveals neurodevelopmental origin of PMM2-CDG brain pathology.bioRxiv : the preprint server for biology · 2025Article
- Targeted metabolomic evaluation of peripheral blood mononucleated cells from patients with PMM2-CDG.Scientific reports · 2025Article
- Goal attainment in PMM2-CDG: A new approach measuring meaningful clinical outcomes.Molecular genetics and metabolism · 2025Article
- Diagnostic and Therapeutic Approaches in Congenital Disorders of Glycosylation.Handbook of experimental pharmacology · 2025Review
- Phosphomannomutase 2-congenital disorder of glycosylation: exploring the role of N-glycosylation on the endocrine axes.Frontiers in endocrinology · 2025Review
- O-GlcNAcylation modulates expression and abundance of N-glycosylation machinery in an inherited glycosylation disorder.Cell reports · 2024Article
- A drug repurposing screen reveals dopamine signaling as a critical pathway underlying potential therapeutics for the rare disease DPAGT1-CDG.PLoS genetics · 2024Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
objectiveEpalrestat, an aldose reductase inhibitor increases phosphomannomutase (PMM) enzyme activity in a PMM2-congenital disorders of glycosylation (CDG) worm model. Epalrestat also decreases sorbitol level in diabetic neuropathy. We evaluated the genetic, biochemical, and clinical characteristics, including the Nijmegen Progression CDG Rating Scale (NPCRS), urine polyol levels and fibroblast glycoproteomics in patients with PMM2-CDG.
methodsWe performed PMM enzyme measurements, multiplexed proteomics, and glycoproteomics in PMM2-deficient fibroblasts before and after epalrestat treatment. Safety and efficacy of 0.8 mg/kg/day oral epalrestat were studied in a child with PMM2-CDG for 12 months.
resultsPMM enzyme activity increased post-epalrestat treatment. Compared with controls, 24% of glycopeptides had reduced abundance in PMM2-deficient fibroblasts, 46% of which improved upon treatment. Total protein N-glycosylation improved upon epalrestat treatment bringing overall glycosylation toward the control fibroblasts' glycosylation profile. Sorbitol levels were increased in the urine of 74% of patients with PMM2-CDG and correlated with the presence of peripheral neuropathy, and CDG severity rating scale. In the child with PMM2-CDG on epalrestat treatment, ataxia scores improved together with significant growth improvement. Urinary sorbitol levels nearly normalized in 3 months and blood transferrin glycosylation normalized in 6 months.
interpretationEpalrestat improved PMM enzyme activity, N-glycosylation, and glycosylation biomarkers in vitro. Leveraging cellular glycoproteome assessment, we provided a systems-level view of treatment efficacy and discovered potential novel biosignatures of therapy response. Epalrestat was well-tolerated and led to significant clinical improvements in the first pediatric patient with PMM2-CDG treated with epalrestat. We also propose urinary sorbitol as a novel biomarker for disease severity and treatment response in future clinical trials in PMM2-CDG. ANN NEUROL 20219999:n/a-n/a.
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