ArticleProceedings of the National Academy of Sciences of the United States of America2014
A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02882477 (Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy), which is not on this map. Cited by 105 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy
Who cites it
105 citing papers in PubMed, 2 syntheses or guidelines pooled it, 148 citations in OpenAlex.
- Modelling mitochondrial diseases in neuronsJournal of neuromuscular diseases · 2025Pooled it
- Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum.International journal of environmental research and public health · 2022Pooled it
- A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome.JCI insight · 2021Trial
- Neuroimaging evidence of deficient axon myelination in Wolfram syndrome.Scientific reports · 2016Trial
- WFS1 gene delivery rescues visual function in a mouse model of Wolfram syndrome.Acta neuropathologica communications · 2026Article
- Evaluating the Use of GLP-1 Receptor Agonists in Wolfram syndrome Patients.medRxiv : the preprint server for health sciences · 2026Article
- Synaptic Alterations Are Preceding the Axonal Loss in Optic Atrophy of Wolfram Syndrome Mouse Model.bioRxiv : the preprint server for biology · 2026Article
- Evaluating the use of GLP-1 receptor agonists in Wolfram syndrome patients.Frontiers in endocrinology · 2026Article
- Synaptic alterations are preceding the axonal loss in optic atrophy of Wolfram syndrome mouse model.Frontiers in neuroscience · 2026Article
- Could R-Ketamine and Wolfram Syndrome Inform Understanding of Depression and Suicidality? A Sigma-1 Receptor-Based Perspective.Human psychopharmacology · 2025Review
- Characterization of Novel WFS1 Variants in Three Diabetes Pedigrees.Journal of diabetes · 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
- Diabetes mellitus and pregnancy in Wolfram syndrome type 1: a case report with review of clinical and pathophysiological aspects.Frontiers in medicine · 2025Article
- ER calcium depletion as a key driver for impaired ER-to-mitochondria calcium transfer and mitochondrial dysfunction in Wolfram syndrome.Nature communications · 2024Article
- Article
- Wolfram Syndrome Type I Case Report and Review-Focus on Early Diagnosis and Genetic Variants.Medicina (Kaunas, Lithuania) · 2024Review
- 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
- ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models.Cell death and differentiation · 2024Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration and considered as an endoplasmic reticulum (ER) disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome and the identification of two causative genes, Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2), a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we implicate calpain 2 in the mechanism of cell death in Wolfram syndrome. Calpain 2 is negatively regulated by WFS2, and elevated activation of calpain 2 by WFS2-knockdown correlates with cell death. Calpain activation is also induced by high cytosolic calcium mediated by the loss of function of WFS1. Calpain hyperactivation is observed in the WFS1 knockout mouse as well as in neural progenitor cells derived from induced pluripotent stem (iPS) cells of Wolfram syndrome patients. A small-scale small-molecule screen targeting ER calcium homeostasis reveals that dantrolene can prevent cell death in neural progenitor cells derived from Wolfram syndrome iPS cells. Our results demonstrate that calpain and the pathway leading its activation provides potential therapeutic targets for Wolfram syndrome and other ER diseases.
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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 OpenQuestion graph.