ArticleDiabetologia2023
GLP-1R agonists demonstrate potential to treat Wolfram syndrome in human preclinical models.
Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Wolfram syndrome and diabetes mellitus in Aotearoa, New Zealand: Phenotype and response to GLP-1 receptor agonist therapy.Diabetic medicine : a journal of the British Diabetic Association · 2026Article
- Consensus Recommendations for the Clinical Management of Wolfram syndrome Using a Delphi Method.medRxiv : the preprint server for health sciences · 2026Article
- Evaluating the Use of GLP-1 Receptor Agonists in Wolfram syndrome Patients.medRxiv : the preprint server for health sciences · 2026Article
- A new form of diabetes caused by INS mutations defined by zygosity, stem cell and population data.EMBO molecular medicine · 2026Article
- The Genetic Landscape and Precision Medicine in Neonatal Diabetes Mellitus: From Molecular Mechanisms to Clinical Management.Current issues in molecular biology · 2026Review
- Evaluating the use of GLP-1 receptor agonists in Wolfram syndrome patients.Frontiers in endocrinology · 2026Article
- Could R-Ketamine and Wolfram Syndrome Inform Understanding of Depression and Suicidality? A Sigma-1 Receptor-Based Perspective.Human psychopharmacology · 2025Review
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Article
- Mitochondria-Associated Membranes: A Key Point of Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2025Review
- Polyethylene Glycol Loxenatide Accelerates Diabetic Wound Healing by Downregulating Systemic Inflammation and Improving Endothelial Progenitor Cell Functions.International journal of molecular sciences · 2025Article
- GABA and GLP-1 receptor agonist combination therapy modifies diabetes and Langerhans islet cytoarchitecture in a rat model of Wolfram syndrome.Diabetology & metabolic syndrome · 2025Article
- Clinical trials for Wolfram syndrome neurodegeneration: Novel design, endpoints, and analysis models.PloS one · 2025Article
- A novel heterozygous WFS1 variant of uncertain significance in a patient with early-onset diabetes: a case report.Frontiers in endocrinology · 2025Article
- Identification of a pathogenic founder variant in theFrontiers in pediatrics · 2025Article
- Paeoniflorin: a review of its pharmacology, pharmacokinetics and toxicity in diabetes.Frontiers in pharmacology · 2025Review
- A deep phenotyping study in mouse and iPSC models to understand the role of oligodendroglia in optic neuropathy in Wolfram syndrome.Acta neuropathologica communications · 2024Article
- Cardiac Wolframinopathies: A Case Report of Myocarditis and a Literature Review of Cardiac Involvement in Wolfram Syndrome 1.Journal of clinical medicine · 2024Review
- Comprehensive overview of disease models for Wolfram syndrome: toward effective treatments.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Review
- Unmasking metabolic disruptors: The NEMESIS project's quest for Novel Biomarkers, Evidence on Adverse Effects, and Efficient Methodologies.Open research Europe · 2024Article
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Authors and funding
25 authors at 4 institutions in 3 countries.
Funding
Abstract
aims/hypothesisWolfram syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the WFS1 gene. It is characterised by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing loss and neurodegeneration. Considering the unmet treatment need for this orphan disease, this study aimed to evaluate the therapeutic potential of glucagon-like peptide 1 receptor (GLP-1R) agonists under wolframin (WFS1) deficiency with a particular focus on human beta cells and neurons.
methodsThe effect of the GLP-1R agonists dulaglutide and exenatide was examined in Wfs1 knockout mice and in an array of human preclinical models of Wolfram syndrome, including WFS1-deficient human beta cells, human induced pluripotent stem cell (iPSC)-derived beta-like cells and neurons from control individuals and individuals affected by Wolfram syndrome, and humanised mice.
resultsOur study shows that the long-lasting GLP-1R agonist dulaglutide reverses impaired glucose tolerance in WFS1-deficient mice, and that exenatide and dulaglutide improve beta cell function and prevent apoptosis in different human WFS1-deficient models including iPSC-derived beta cells from people with Wolfram syndrome. Exenatide improved mitochondrial function, reduced oxidative stress and prevented apoptosis in Wolfram syndrome iPSC-derived neural precursors and cerebellar neurons. CONCLUSIONS/
interpretationOur study provides novel evidence for the beneficial effect of GLP-1R agonists on WFS1-deficient human pancreatic beta cells and neurons, suggesting that these drugs may be considered as a treatment for individuals with Wolfram syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.