ArticleJCI insight2022
Multidimensional analysis and therapeutic development using patient iPSC-derived disease models of Wolfram syndrome.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 29 citations in OpenAlex.
- Metabolic Programming of β-Cell Fate, State, and Function through Time and Space.Physiology (Bethesda, Md.) · 2026Review
- Ghrelin and relamorelin counteract hypoglycemia in mice engrafted with congenital hyperinsulinism stem cell-derived islets.Stem cells translational medicine · 2026Article
- Consensus Recommendations for the Clinical Management of Wolfram syndrome Using a Delphi Method.medRxiv : the preprint server for health sciences · 2026Article
- Wolfram syndrome: A perspective on gene editing as a therapeutic strategy.Neural regeneration research · 2026Article
- Genotype-Based Severity Scoring System in Wolfram Syndrome: Correlation with Onset of Cardinal Symptoms andmedRxiv : the preprint server for health sciences · 2026Article
- Phase II trial of sodium phenylbutyrate and taurursodiol in Wolfram syndrome.The Journal of clinical investigation · 2026Article
- Use of Small Organic Molecules to Improve Pancreatic Beta Cell Resilience to IAPP-Induced Proteotoxic Stress.International journal of molecular sciences · 2026Review
- Evaluating the use of GLP-1 receptor agonists in Wolfram syndrome patients.Frontiers in endocrinology · 2026Article
- Genotype-based severity scoring system in Wolfram Syndrome: correlation with onset of cardinal symptoms andFrontiers in genetics · 2026Article
- Coxsackievirus B infection invokes unique cell-type-specific responses in primary human pancreatic islets.Cell reports · 2025Article
- Circadian Rhythm and Psychiatric Features in Wolfram Syndrome: Toward Chrono Diagnosis and Chronotherapy.Diagnostics (Basel, Switzerland) · 2025Article
- Article
- 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
- Expanding the spectrum of white matter abnormalities in Wolfram syndrome: a retrospective review.Frontiers in neurology · 2025Article
- A WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on beta cell apoptosis in a patient with Wolfram syndrome.Diabetologia · 2025Article
- The perfect storm: unraveling the interplay of genetic predisposition and viral triggers in type 1 diabetes pathogenesis.Frontiers in endocrinology · 2025Review
- Recent progress in modeling and treating diabetes using stem cell-derived islets.Stem cells translational medicine · 2024Review
- Identification of unique cell type responses in pancreatic islets to stress.Nature communications · 2024Article
- The hope, hype and obstacles surrounding cell therapy.Journal of cellular and molecular medicine · 2024Review
- Comprehensive overview of disease models for Wolfram syndrome: toward effective treatments.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Review
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Wolfram syndrome is a rare genetic disorder largely caused by pathogenic variants in the WFS1 gene and manifested by diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Recent genetic and clinical findings have revealed Wolfram syndrome as a spectrum disorder. Therefore, a genotype-phenotype correlation analysis is needed for diagnosis and therapeutic development. Here, we focus on the WFS1 c.1672C>T, p.R558C variant, which is highly prevalent in the Ashkenazi Jewish population. Clinical investigation indicated that patients carrying the homozygous WFS1 c.1672C>T, p.R558C variant showed mild forms of Wolfram syndrome phenotypes. Expression of WFS1 p.R558C was more stable compared with the other known recessive pathogenic variants associated with Wolfram syndrome. Human induced pluripotent stem cell-derived (iPSC-derived) islets (SC-islets) homozygous for WFS1 c.1672C>T variant recapitulated genotype-related Wolfram syndrome phenotypes. Enhancing residual WFS1 function through a combination treatment of chemical chaperones mitigated detrimental effects caused by the WFS1 c.1672C>T, p.R558C variant and increased insulin secretion in SC-islets. Thus, the WFS1 c.1672C>T, p.R558C variant causes a mild form of Wolfram syndrome phenotypes, which can be remitted with a combination treatment of chemical chaperones. We demonstrate that our patient iPSC-derived disease model provides a valuable platform for further genotype-phenotype analysis and therapeutic development for Wolfram syndrome.
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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 OpenQuestion graph.